Histology and ultrastructure of transitional changes in skin morphology in the juvenile and adult four-striped mouse (Rhabdomys pumilio).

PubMed

Stewart, Eranée; Ajao, Moyosore Salihu; Ihunwo, Amadi Ogonda

2013-01-01

The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. In both the juvenile and adult four-striped mouse, pigment-containing cells were observed in the dermis and were homogeneously dispersed throughout this layer. Apart from these cells, the histology of the skin of the adult four-striped mouse was similar to normal mammalian skin. In the juvenile four-striped mouse, abundant hair follicles of varying sizes were observed in the dermis and hypodermis, while hair follicles of similar size were only present in the dermis of adult four-striped mouse. Ultrastructural analysis of juvenile hair follicles revealed that the arrangement and differentiation of cellular layers were typical of a mammal. This study therefore provides unique transition pattern in the four-striped mouse skin morphology different from the textbook description of the normal mammalian skin.

Regenerative metamorphosis in hairs and feathers: follicle as a programmable biological printer

PubMed Central

Oh, Ji Won; Lin, Sung-Jan; Plikus, Maksim V.

2015-01-01

Present-day hairs and feathers are marvels of biological engineering perfected over 200 million years of convergent evolution. Prominently, both follicle types coevolved regenerative cycling, wherein active filament making (anagen) is intermitted by a phase of relative quiescence (telogen). Such regenerative cycling enables follicles to “reload” their morphogenetic program and make qualitatively different filaments in the consecutive cycles. Indeed, many species of mammals and birds undergo regenerative metamorphosis, prominently changing their integument between juvenile and adult forms. This phenomenon is inconspicuous in mice, which led to the conventional perception that hair type is hardwired during follicle morphogenesis and cannot switch. A series of recent works by Chi and Morgan change this perception, and show that many mouse follicles naturally switch hair morphologies, for instance from “wavy” zigzag to straight awl, in the second growth cycle. A series of observations and genetic experiments show that back and forth hair type switching depends on the number of cells in the follicle's dermal papilla, with the critical threshold being around 40-50 cells. Pigmentation is another parameter that hair and feather follicles can reload between cycles, and even midway through anagen. Recent works show that hair and feather pigmentation “printing” programs coevolved to rely on pulsed expression of Agouti, a melanocortin receptor-1 antagonist, in the follicular mesenchyme. Here, we discuss broader implications of hair and feather regenerative plasticity. PMID:25557541

Notch Signaling Regulates Late-Stage Epidermal Differentiation and Maintains Postnatal Hair Cycle Homeostasis

PubMed Central

Lin, Hsien-Yi; Kao, Cheng-Heng; Lin, Kurt Ming-Chao; Kaartinen, Vesa; Yang, Liang-Tung

2011-01-01

Background Notch signaling involves ligand-receptor interactions through direct cell-cell contact. Multiple Notch receptors and ligands are expressed in the epidermis and hair follicles during embryonic development and the adult stage. Although Notch signaling plays an important role in regulating differentiation of the epidermis and hair follicles, it remains unclear how Notch signaling participates in late-stage epidermal differentiation and postnatal hair cycle homeostasis. Methodology and Principal Findings We applied Cre/loxP system to generate conditional gene targeted mice that allow inactivation of critical components of Notch signaling pathway in the skin. Rbpj, the core component of all four Notch receptors, and Pofut1, an essential factor for ligand-receptor interactions, were inactivated in hair follicle lineages and suprabasal layer of the epidermis using the Tgfb3-Cre mouse line. Rbpj conditional inactivation resulted in granular parakeratosis and reactive epidermal hyperplasia. Pofut1 conditional inactivation led to ultrastructural abnormalities in the granular layer and altered filaggrin processing in the epidermis, suggesting a perturbation of the granular layer differentiation. Disruption of Pofut1 in hair follicle lineages resulted in aberrant telogen morphology, a decrease of bulge stem cell markers, and a concomitant increase of K14-positive keratinocytes in the isthmus of mutant hair follicles. Pofut1-deficent hair follicles displayed a delay in anagen re-entry and dysregulation of proliferation and apoptosis during the hair cycle transition. Moreover, increased DNA double stand breaks were detected in Pofut1-deficent hair follicles, and real time PCR analyses on bulge keratinocytes isolated by FACS revealed an induction of DNA damage response and a paucity of DNA repair machinery in mutant bulge keratinocytes. Significance our data reveal a role for Notch signaling in regulating late-stage epidermal differentiation. Notch signaling is required for postnatal hair cycle homeostasis by maintaining proper proliferation and differentiation of hair follicle stem cells. PMID:21267458

Widespread porokeratotic adnexal ostial nevus: clinical features and proposal of a new name unifying porokeratotic eccrine ostial and dermal duct nevus and porokeratotic eccrine and hair follicle nevus.

PubMed

Goddard, Deborah S; Rogers, Maureen; Frieden, Ilona J; Krol, Alfons L; White, Clifton R; Jayaraman, Anu G; Robinson-Bostom, Leslie; Bruckner, Anna L; Ruben, Beth S

2009-12-01

Porokeratotic eccrine ostial and dermal duct nevus and a similar condition, porokeratotic eccrine and hair follicle nevus, are rare disorders of keratinization with eccrine and hair follicle involvement. We describe the clinical features in 5 patients, all of whom had widespread skin involvement following the lines of Blaschko. Two patients presented with erosions in the newborn period as the initial manifestation of their disease; one had an associated structural anomaly, unilateral breast hypoplasia; and one adult had malignant transformation in the nevus with development of multifocal squamous cell carcinomas. Three patients had histologic involvement of both acrosyringia and acrotrichia. Based on the observation of overlapping histologic features, we propose the name "porokeratotic adnexal ostial nevus" to incorporate the previously described entities porokeratotic eccrine ostial and dermal duct nevus and porokeratotic eccrine and hair follicle nevus.

Cryopreservation of Hair-Follicle Associated Pluripotent (HAP) Stem Cells Maintains Differentiation and Hair-Growth Potential.

PubMed

Hoffman, Robert M; Kajiura, Satoshi; Cao, Wenluo; Liu, Fang; Amoh, Yasuyuki

2016-01-01

Hair follicles contain nestin-expressing pluripotent stem cells which originate above the bulge area of the follicle, below the sebaceous gland. We have termed these cells hair follicle-associated pluripotent (HAP) stem cells. We have established efficient cryopreservation methods of the hair follicle that maintain the pluripotency of HAP stem cells as well as hair growth. We cryopreserved the whole hair follicle by slow-rate cooling in TC-Protector medium or in DMSO-containing medium and storage in liquid nitrogen or at -80 °C. After thawing and culture of the cryopreserved whisker follicles, growing HAP stem cells formed hair spheres. The hair spheres contained cells that differentiated to neurons, glial cells, and other cell types. The hair spheres derived from slow-cooling cryopreserved hair follicles were as pluripotent as hair spheres from fresh hair follicles. We have also previously demonstrated that cryopreserved mouse whisker hair follicles maintain their hair-growth potential. DMSO better cryopreserved mouse whisker follicles compared to glycerol. DMSO-cryopreserved hair follicles also maintained the HAP stem cells, evidenced by P75 ntr expression. Subcutaneous transplantation of DMSO-cryopreserved hair follicles in nude mice resulted in extensive hair fiber growth over 8 weeks, indicating the functional recovery of hair-shaft growth of cryopreserved hair follicles. HAP stem cells can be used for nerve and spinal-cord repair. This biobanking of hair follicles can allow each patient the potential for their own stem cell use for regenerative medicine or hair transplantation.

Preliminary analysis of facial hair follicle distribution for forensic identification using OCT

NASA Astrophysics Data System (ADS)

Zhang, Ning; Wang, Chengming; Li, Zhigang; Xie, Lanchi; Guo, Jingjing; Xu, Lei; Yan, Yuwen; Li, Zhihui; Huang, Wei; Xu, Xiaojing

2018-02-01

In most deaths caused by explosions, the fragment of explosive remained on the victim's body can provide valuable clues to forensic investigation. However, the examination of the skin and appendages at the scene of explosion, which may reveal clue to the identity of an individual, has not been extensively studied. Compared with visual appearance of the epidermis surface that affected by various wounds, skin adnexa embedded in the dermis has a more stable morphology as an inner biometric. Hair follicles are formed when a fetus is 5 months old and distributed fairly evenly throughout the body, with the exception of hairless palms and soles. Therefore, we focus on the distribution of hair follicles in order to infer information of age, gender, and race/ethnicity. Optical coherence tomography (OCT) is a novel forensic imaging method, which achieves non-destructive, high-resolution and most importantly cross-sectional imaging. In this study, we design and develop a custom-built spectral-domain three-dimensional (3D) OCT system with a portable handheld probe to detect and reconstruct the hair follicles in the facial skin. We test our system on the forehead and preauricular skin of 2 adult volunteers and demonstrate the high quality visualization of hair follicles beneath the epidermis. The diameter, orientation, density and shape of hair follicles can be extracted from the 3D volume data. The preliminary analysis suggests that these parameters vary from different part of body and have individual difference. Eventually, we believe 3D OCT is promising tool for the examination of hair follicles for forensic purpose.

Extensive Hair Shaft Growth after Mouse Whisker Follicle Isolation, Cryopreservation and Transplantation in Nude Mice

PubMed Central

Cao, Wenluo; Li, Lingna; Tran, Benjamin; Kajiura, Satoshi; Amoh, Yasuyuki; Liu, Fang; Hoffman, Robert M.

2015-01-01

We previously demonstrated that whole hair follicles could be cryopreserved to maintain their stem-cells differentation potential. In the present study, we demonstrated that cryopreserved mouse whisker hair follicles maintain their hair growth potential. DMSO better cryopreserved mouse whisker follicles compared to glycerol. Cryopreserved hair follicles also maintained the hair follicle-associated-pluripotent (HAP) stem cells, evidenced by P75NTR expression. Subcutaneous transplantation of DMSO-cryopreserved hair follicles in nude mice resulted in extensive hair fiber growth over 8 weeks, indicating the functional recovery of hair shaft growth of cryopreserved hair follicles. PMID:26716690

Extensive Hair Shaft Growth after Mouse Whisker Follicle Isolation, Cryopreservation and Transplantation in Nude Mice.

PubMed

Cao, Wenluo; Li, Lingna; Tran, Benjamin; Kajiura, Satoshi; Amoh, Yasuyuki; Liu, Fang; Hoffman, Robert M

2015-01-01

We previously demonstrated that whole hair follicles could be cryopreserved to maintain their stem-cells differentation potential. In the present study, we demonstrated that cryopreserved mouse whisker hair follicles maintain their hair growth potential. DMSO better cryopreserved mouse whisker follicles compared to glycerol. Cryopreserved hair follicles also maintained the hair follicle-associated-pluripotent (HAP) stem cells, evidenced by P75NTR expression. Subcutaneous transplantation of DMSO-cryopreserved hair follicles in nude mice resulted in extensive hair fiber growth over 8 weeks, indicating the functional recovery of hair shaft growth of cryopreserved hair follicles.

The hair follicle bulge: a niche for adult stem cells.

PubMed

Pasolli, Hilda Amalia

2011-08-01

Adult stem cells (SCs) are essential for tissue homeostasis and wound repair. They have the ability to both self-renew and differentiate into multiple cell types. They often reside in specialized microenvironments or niches that preserve their proliferative and tissue regenerative capacity. The murine hair follicle (HF) has a specialized and permanent compartment--the bulge, which safely lodges SCs and provides the necessary molecular cues to regulate their function. The HF undergoes cyclic periods of destruction, regeneration, and rest, making it an excellent system to study SC biology.

Bulge Hair Follicle Stem Cells Accelerate Cutaneous Wound Healing in Rats.

PubMed

Heidari, Fatemeh; Yari, Abazar; Rasoolijazi, Homa; Soleimani, Mansoureh; Dehpoor, Ahmadreza; Sajedi, Nayereh; Joulai Veijouye, Sanaz; Nobakht, Maliheh

2016-04-01

Skin wound healing is a serious clinical problem especially after surgery and severe injury of the skin. Cell therapy is an innovative technique that can be applied to wound healing. One appropriate source of stem cells for therapeutic use is stem cells from the adult bulge of hair follicles. This study examined the effects of adult bulge hair follicle stem cells (HFSC) in wound healing. Hair follicle stem cells were obtained from rat vibrissa and labeled with DiI (Invitrogen, Carlsbad, CA), then special markers were detected using flow cytometry. A full-thickness excisional wound model was created and DiI-labeled HFSC were injected around the wound bed. Wound healing was recorded with digital photographs. Animals were sacrificed at 3, 7, or 14 days after surgery, and were used for the following histological analyses. Flow cytometry analysis showed that HFSC were CD34 positive and nestin positive, but K15 negative. Morphological analysis of HFSC-treated wounds exhibited accelerated wound closure. Histological analysis of hematoxylin and eosin stained and Masson's trichrome-stained photomicrographs showed significantly more re-epithelialization and dermal structural regeneration in HFSC-treated wounds than in the control group. Immunohistochemical analysis of CD31 protein-positive cells showed angiogenesis was also more significant in HFSC-treated wounds than in the control group. Hair follicle stem cells accelerate skin wound healing. Isolating HFSC from a small skin biopsy could repair less-extensive full-thickness skin wounds by autologous stem cells and overcome major challenges regarding the use of stem cells in clinical application, while avoiding immune rejection and ethical concerns.

Reflectance spectroscopy for evaluating hair follicle cycle

NASA Astrophysics Data System (ADS)

Liu, Caihua; Guan, Yue; Wang, Jianru; Zhu, Dan

2014-02-01

Hair follicle, as a mini-organ with perpetually cycling of telogen, anagen and catagen, provides a valuable experimental model for studying hair and organ regeneration. The transition of hair follicle from telogen to anagen is a significant sign for successful regeneration. So far discrimination of the hair follicle stage is mostly based on canonical histological examination and empirical speculation based on skin color. Hardly a method has been proposed to quantitatively evaluate the hair follicle stage. In this work, a commercial optical fiber spectrometer was applied to monitor diffuse reflectance of mouse skin with hair follicle cycling, and then the change of reflectance was obtained. Histological examination was used to verify the hair follicle stage. In comparison with the histological examination, the skin diffuse reflectance was relatively high for mouse with telogen hair follicles; it decreased once hair follicles transited to anagen stage; then it increased reversely at catagen stage. This study provided a new method to quantitatively evaluate the hair follicle stage, and should be valuable for the basic and therapeutic investigations on hair regeneration.

Morphological analysis of the growth stages of in-vivo mouse hair follicles by using optical coherence tomography

NASA Astrophysics Data System (ADS)

Jha, Rakesh Kumar; Kim, Kanghae; Jeon, Mansik; Kim, Jeehyun; Kang, Minyoung; Han, Insook; Kim, Moonkyu

2016-09-01

Swept-source optical coherence tomography (SS-OCT), a bio-photonic imaging modality, was used to demonstrate an initial feasibility experiment for detecting morphological variations of in-vivo mouse hair follicles for the anagen and the telogen growth stages. Two C57BL/6 adult male mice, one undergoing the anagen stage and the other undergoing the telogen stage of the hair follicle growth cycle, were selected for the experiment. The OCT cross-sectional images of mice skin were acquired in-vivo within an interval of 15 days, and the observed morphological changes were analyzed. The micro-structural features of mice skin on the 15th experimental day were further compared with corresponding histological observations. The preliminary result of this study provides clear insights into the structural details of mouse skin, confirming the resemblance of the OCT images with the corresponding histological measurements, and ensures the suitability of SS-OCT for non-invasive analysis of hair follicle conditions.

Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration.

PubMed

Qiu, Weiming; Lei, Mingxing; Zhou, Ling; Bai, Xiufeng; Lai, Xiangdong; Yu, Yu; Yang, Tian; Lian, Xiaohua

2017-06-01

Regeneration of hair follicles relies on activation of hair follicle stem cells during telogen to anagen transition process in hair cycle. This process is rigorously controlled by intrinsic and environmental factors. 12-o-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, accelerates reentry of hair follicles into anagen phase. However, it is unclear that how TPA promotes the hair regeneration. In the present study, we topically applied TPA onto the dorsal skin of 2-month-old C57BL/6 female mice to examine the activity of hair follicle stem cells and alteration of signaling pathways during hair regeneration. We found that refractory telogen hair follicles entered anagen prematurely after TPA treatment, with the enhanced proliferation of CD34-positive hair follicle stem cells. Meanwhile, we observed Akt signaling was activated in epidermis, hair infundibulum, bulge and hair bulb, and Wnt signaling was also activated after hair follicle stem cells proliferation. Importantly, after overexpression of DKK1, a specific Wnt signaling inhibitor, the accelerated reentry of hair follicles into anagen induced by TPA was abolished. Our data indicated that TPA-induced hair follicle regeneration is associated with activation of Akt and Wnt/β-catenin signaling.

Epidermal E-Cadherin Dependent β-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling.

PubMed

Ahmed, Noha S; Ghatak, Subhadip; El Masry, Mohamed S; Gnyawali, Surya C; Roy, Sashwati; Amer, Mohamed; Everts, Helen; Sen, Chandan K; Khanna, Savita

2017-11-01

Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. This was observed in the skin of healthy as well as diabetic mice, which are known to be resistant to anagen hair cycling. TRF suppressed epidermal E-cadherin followed by 4-fold induction of β-catenin and its nuclear translocation. Nuclear β-catenin interacted with Tcf3. Such sequestration of Tcf3 from its otherwise known function to repress pluripotent factors induced the plasticity factors Oct4, Sox9, Klf4, c-Myc, and Nanog. Pharmacological inhibition of β-catenin arrested anagen hair cycling by TRF. This work reports epidermal E-cadherin/β-catenin as a novel pathway capable of inducing developmental folliculogenesis in the adult skin. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Central anatomy of individual rapidly adapting low-threshold mechanoreceptors innervating the "hairy" skin of newborn mice: early maturation of hair follicle afferents.

PubMed

Woodbury, C J; Ritter, A M; Koerber, H R

2001-07-30

Adult skin sensory neurons exhibit characteristic projection patterns in the dorsal horn of the spinal gray matter that are tightly correlated with modality. However, little is known about how these patterns come about during the ontogeny of the distinct subclasses of skin sensory neurons. To this end, we have developed an intact ex vivo somatosensory system preparation in neonatal mice, allowing single, physiologically identified cutaneous afferents to be iontophoretically injected with Neurobiotin for subsequent histological analyses. The present report, centered on rapidly adapting mechanoreceptors, represents the first study of the central projections of identified skin sensory neurons in neonatal animals. Cutaneous afferents exhibiting rapidly adapting responses to sustained natural stimuli were encountered as early as recordings were made. Well-stained representatives of coarse (tylotrich and guard) and fine-diameter (down) hair follicle afferents, along with a putative Pacinian corpuscle afferent, were recovered from 2-7-day-old neonates. All were characterized by narrow, uninflected somal action potentials and generally low mechanical thresholds, and many could be activated via deflection of recently erupted hairs. The central collaterals of hair follicle afferents formed recurrent, flame-shaped arbors that were essentially miniaturized replicas of their adult counterparts, with identical laminar terminations. The terminal arbors of down hair afferents, previously undescribed in rodents, were distinct and consistently occupied a more superficial position than tylotrich and guard hair afferents. Nevertheless, the former extended no higher than the middle of the incipient substantia gelatinosa, leaving a clear gap more dorsally. In all major respects, therefore, hair follicle afferents display the same laminar specificity in neonates as they do in adults. The widely held misperception that their collaterals extend exuberant projections into pain-specific regions of the dorsal horn during early postnatal life is shown to have multiple, deep-rooted underpinnings.

The biology, structure, and function of eyebrow hair.

PubMed

Nguyen, Jennifer V

2014-01-01

Eyebrow hair serves many important biologic and aesthetic functions. This article reviews the structure and function of the hair follicle, as well as hair follicle morphogenesis and cycling. Eyebrow hair follicles share the same basic structure as hair follicles elsewhere on the body, but are distinguished by their shorter anagen (growing) phase. Knowledge of the hair follicle structure and cycle is important for understanding the pathophysiology of alopecia, as diseases affecting the stem cell portion of the hair follicle in the bulge region may cause permanent hair loss. Furthermore, therapeutic agents that target distinct phases and hormones involved in the hair cycle may be useful for promoting hair growth.

CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth

PubMed Central

Zhou, Linli; Yang, Kun; Carpenter, April; Lang, Richard A.; Andl, Thomas; Zhang, Yuhang

2016-01-01

Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment. PMID:27462123

Effects of in utero retinoic acid exposure on mouse pelage hair follicle development.

PubMed

García-Fernández, Rosa A; Pérez-Martínez, Claudia; Escudero-Diez, Alfredo; García-Iglesias, Maria J

2002-06-01

We investigated in vivo the histological and immunohistochemical responses of mouse hair pelage follicle morphogenesis to prenatal exposure to a potentially nonteratogenic dose of all-trans-retinoic acid (RA), as a basis studying the preventive effect of RA on adult mouse skin carcinogenesis. In pregnant mice, a single oral dose of RA at 30 mg kg-1 body weight given on day 11.5 of gestation caused no RA-induced changes in the morphology or temporal expression patterns of keratins during pelage hair follicle morphogenesis. The only differential effect of RA was a statistically significant increase in the number of BrdU-positive nuclei in hair bulbs from RA exposed fetuses compared with nonexposed mice. The absence of adverse RA effects suggests that this experimental design may represent a valuable protocol for use in studies on the in vivo effects of this retinoid on different skin diseases.

Hair Follicle Generation by Injections of Adult Human Follicular Epithelial and Dermal Papilla Cells into Nude Mice

PubMed Central

Nilforoushzadeh, Mohammadali; Rahimi Jameh, Elham; Jaffary, Fariba; Abolhasani, Ehsan; Keshtmand, Gelavizh; Zarkob, Hajar; Mohammadi, Parvaneh; Aghdami, Nasser

2017-01-01

Objective Dermal papilla and hair epithelial stem cells regulate hair formation and the growth cycle. Damage to or loss of these cells can cause hair loss. Although several studies claim to reconstitute hairs using rodent cells in an animal model, additional research is needed to develop a stable human hair follicle reconstitution protocol. In this study, we have evaluated hair induction by injecting adult cultured human dermal papilla cells and a mixture of hair epithelial and dermal papilla cells in a mouse model. Materials and Methods In this experimental study, discarded human scalp skins were used to obtain dermal papilla and hair epithelial cells. After separation, cells were cultured and assessed for their characteristics. We randomly allocated 15 C57BL/6 nude mice into three groups that received injections in their dorsal skin. The first group received cultured dermal papilla cells, the second group received a mixture of cultured epithelial and dermal papilla cells, and the third group (control) received a placebo [phosphate-buffered saline (PBS-)]. Results Histopathologic examination of the injection sites showed evidence of hair growth in samples that received cells compared with the control group. However, the group that received epithelial and dermal papilla cells had visible evidence of hair growth. PKH tracing confirmed the presence of transplanted cells in the new hair. Conclusion Our data showed that injection of a combination of adult human cultured dermal papilla and epithelial cells could induce hair growth in nude mice. This study emphasized that the combination of human adult cultured dermal papilla and epithelial cells could induce new hair in nude mice. PMID:28670518

Activin B promotes initiation and development of hair follicles in mice.

PubMed

Jia, Qin; Zhang, Min; Kong, Yanan; Chen, Shixuan; Chen, Yinghua; Wang, Xueer; Zhang, Lei; Lang, Weiya; Zhang, Lu; Zhang, Lin

2013-01-01

Activin B has been reported to promote the regeneration of hair follicles during wound healing. However, its role in the development and life cycle of hair follicles has not been elucidated. In our study, the effect of activin B on mouse hair follicles of cultured and neonatal mouse skin was investigated. In these models, PBS or activin B (5, 10 or 50 ng/ml) was applied, and hair follicle development was monitored. Hair follicle initiation and development was examined using hematoxylin and eosin staining, alkaline phosphatase activity staining, Oil Red O+ staining, and the detection of TdT-mediated dUTP-biotin nick end-labeling cell apoptosis. Activin B was found to efficiently induce the initiation of hair follicles in the skin of both cultured and neonatal mice and to promote the development of hair follicles in neonatal mouse skin. Moreover, activin-B-treated hair follicles were observed to enter the anagen stage from the telogen stage and to remain in the anagen stage. These results demonstrate that activin B promotes the initiation and development of hair follicles in mice.

Exogenous R-Spondin1 Induces Precocious Telogen-to-Anagen Transition in Mouse Hair Follicles

PubMed Central

Li, Na; Liu, Shu; Zhang, Hui-Shan; Deng, Zhi-Li; Zhao, Hua-Shan; Zhao, Qian; Lei, Xiao-Hua; Ning, Li-Na; Cao, Yu-Jing; Wang, Hai-Bin; Liu, Shuang; Duan, En-Kui

2016-01-01

R-spondin proteins are novel Wnt/β-catenin agonists, which signal through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR) 4/5/6 and substantially enhance Wnt/β-catenin activity. R-spondins are reported to function in embryonic development. They also play important roles in stem cell functions in adult tissues, such as the intestine and mammary glands, which largely rely on Wnt/β-catenin signaling. However, in the skin epithelium and hair follicles, the information about R-spondins is deficient, although the expressions and functions of their receptors, LGR4/5/6, have already been studied in detail. In the present study, highly-enriched expression of the R-spondin family genes (Rspo1/2/3/4) in the hair follicle dermal papilla is revealed. Expression of Rspo1 in the dermal papilla is specifically and prominently upregulated before anagen entry, and exogenous recombinant R-spondin1 protein injection in mid-telogen leads to precocious anagen entry. Moreover, R-spondin1 activates Wnt/β-catenin signaling in cultured bulge stem cells in vitro, changing their fate determination without altering the cell proliferation. Our pioneering study uncovers a role of R-spondin1 in the activation of cultured hair follicle stem cells and the regulation of hair cycle progression, shedding new light on the governance of Wnt/β-catenin signaling in skin biology and providing helpful clues for future treatment of hair follicle disorders. PMID:27104524

CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth.

PubMed

Zhou, Linli; Yang, Kun; Carpenter, April; Lang, Richard A; Andl, Thomas; Zhang, Yuhang

2016-10-01

Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Disruption of the hedgehog signaling pathway contributes to the hair follicle cycling deficiency in Vdr knockout mice.

PubMed

Teichert, Arnaud; Elalieh, Hashem; Bikle, Daniel

2010-11-01

Mice null for the Vitamin D receptor (VdrKO) have a disrupted first hair follicle cycle and aborted subsequent hair follicle cycling. We examined the expression of different markers and mediators of hair follicle cycling in the hair follicle of the VdrKO mouse during days 13-22 when the hair follicle normally initiates and completes the first catagen. We compared the expression of those genes in mice with a nonsense mutation in hairless (Rhino), which have a similar alopecia phenotype, and to Cyp27b1 null mice which are deficient in the production of 1,25(OH)2D3, the Vdr ligand, but display normal hair follicle cycling. Our results demonstrate the down regulation of hair follicle markers and the alteration of expression of hedgehog (Hh), Wnt, Fgf, and Tgfbeta pathways in VdrKO and Rhino mice, but not in Cyp27b1KO mice. Treatment of VdrKO mice with an agonist to the Hh pathway partially restored hair follicle cycling, suggesting a role of this pathway in the regulation of hair follicle cycling by VDR. These results suggest that Vdr regulates directly or indirectly the expression of genes required for hair follicle cycling, including Hh signaling, independent of 1,25(OH)2D3. (c) 2010 Wiley-Liss, Inc.

Modulating hair follicle size with Wnt10b-DKK1 pair during hair regeneration

PubMed Central

Lei, Mingxing; Guo, Haiying; Qiu, Weiming; Lai, Xiangdong; Yang, Tian; Widelitz, Randall B.; Chuong, Cheng-Ming; Lian, Xiaohua; Yang, Li

2015-01-01

Hair follicles have characteristic sizes corresponding to their cycle specific stage. However, how the anagen hair follicle specifies its size remains elusive. Here, we show that in response to prolonged ectopic Wnt10b-mediated β-catenin activation, regenerating anagen hair follicles grow larger in size. In particular, the hair bulb, dermal papilla and hair shaft become enlarged. While the formation of different hair types (Guard, Awl, Auchene, and Zigzag) is unaffected. Interestingly, we found the effect of exogenous WNT10b was mainly on Zigzag and less on the other kinds of hairs. We observed dramatically enhanced proliferation within the matrix, DP and hair shaft of the enlarged AdWnt10b-treated hair follicles compared with those of normal hair follicles at P98. Furthermore, expression of CD34, a specific hair stem cell marker, was increased in its number to the bulge region after AdWnt10b treatment. Ectopic expression of CD34 throughout the ORS region was also observed. Many CD34 positive hair stem cells were actively proliferating in AdWnt10b-induced hair follicles. Importantly, subsequent co-treatment with the Wnt inhibitor, DKK1, reduced hair follicle enlargement, decreased proliferation and maintained proper hair stem cell localization. Moreover, injection of DKK1 during early anagen significantly reduced the width of prospective hairs. Together, these findings strongly suggest that a balance of Wnt10b/DKK1 governs reciprocal signaling between cutaneous epithelium and mesenchyme to regulate proper hair follicle size. PMID:24750467

Hair-cycle dependent differential expression of ADAM 10 and ADAM 12

PubMed Central

Cho, Baik-Kee; Schramme, Anja; Gutwein, Paul; Tilgen, Wolfgang; Reichrath, Jörg

2009-01-01

Background ADAM proteases play important roles in processes of development and differentiation. However, no report has been found in the literature addressing the expression and function of ADAM proteases during hair cycling. Results Cytoplasmic expression pattern of ADAM 10, 12 was similar between normal epidermis and hair infundibulum. In addition, cytoplasmic expression of ADAM 10 was observed in the hair bulb keratinocytes and fibroblasts of dermal papilla in anagen I–III hair follicles. In contrast, decreased ADAM 10 expression was observed in the hair matrix keratinocytes as compared to the hair bulb keratinocytes in anagen I–III hair follicles. Interestingly, ADAM 10 immunoreactivity was expressed weakly in the lower portion of outer root sheath (ORS) of anagen VI hair follicles, and strong ADAM 10 expression was detected in the ORS of catagen and telogen hair follicles. By contrast, ADAM 12 expression was not detected in the hair bulb keratinocytes of anagen I–III hair follicles. ADAM 12 immunoreactivity firstly appeared in the inner root sheath ( IRS ) of anagen IV—V hair follicles and was down-regulated in the IRS and hair cortex and medulla of catagen hair follicles, Strong ADAM 12 immunoreactivity was observed in the ORS of catagen and telogen hair follicles. Material and methods Samples of normal human skin (n = 30) were used. Immunohistochemical analysis was performed using ADAM 10, 12 specific polyclonal antibodies and a sensitive streptavidin-peroxidase technique. Conclusion Our study demonstrates a comparable staining pattern of decreased ADAM 10 immunoreactivity in hair matrix keratinocytes and the basal cell layer of normal epidermis and hair infundibulum. Expression of ADAM 10 in dermal papilla cells may imply a role in the induction and development of anagen hair follicles. In addition, expression of ADAM 10 in the ORS and hair bulb assume the involvment of ADAM 10 in the downward migration of anagen hair follicles. Furthermore ADAM 12 expression in the IRS may indicate a role in the differentiation of anagen hair follicles. Downregulation of ADAM 12 upon the onset of catagen hair stage suggests that ADAM 12 may play an important role of ADAM 12 in the apoptosis of hair follicle keratinocytes. In summary our findings suggest that ADAM 10 and 12 may be of importance for the regulation of hair cycling. PMID:20046589

Therapeutic strategy for hair regeneration: Hair cycle activation, niche environment modulation, wound-induced follicle neogenesis and stem cell engineering

PubMed Central

Chueh, Shan-Chang; Lin, Sung-Jan; Chen, Chih-Chiang; Lei, Mingxing; Wang, Ling Mei; Widelitz, Randall B.; Hughes, Michael W.; Jiang, Ting-Xing; Chuong, Cheng Ming

2013-01-01

Introduction There are major new advancements in the fields of stem cell biology, developmental biology, regenerative hair cycling, and tissue engineering. The time is ripe to integrate, translate and apply these findings to tissue engineering and regenerative medicine. Readers will learn about new progress in cellular and molecular aspects of hair follicle development, regeneration and potential therapeutic opportunities these advances may offer. Areas covered Here we use hair follicle formation to illustrate this progress and to identify targets for potential strategies in therapeutics. Hair regeneration is discussed in four different categories. (1) Intra-follicle regeneration (or renewal) is the basic production of hair fibers from hair stem cells and dermal papillae in existing follicles. (2) Chimeric follicles via epithelial-mesenchymal recombination to identify stem cells and signaling centers. (3) Extra-follicular factors including local dermal and systemic factors can modulate the regenerative behavior of hair follicles, and may be relatively easy therapeutic targets. (4) Follicular neogenesis means the de novo formation of new follicles. In addition, scientists are working to engineer hair follicles, which require hair forming competent epidermal cells and hair inducing dermal cells. Expert opinion Ideally self-organizing processes similar to those occurring during embryonic development should be elicited with some help from biomaterials. PMID:23289545

Expression and localization of VEGFR-2 in hair follicles during induced hair growth in mice.

PubMed

Wu, Xian-Jie; Jing, Jing; Lu, Zhong-Fa; Zheng, Min

2018-06-16

Recently, VEGFR-2 has been detected not only in vascular and lymphatic endothelial cells but also in some non-vascular endothelial cells, particularly human hair follicles, sebaceous glands, and sweat glands. In addition, VEGFR-2 has been confirmed to play direct roles in hair follicle keratinocyte regulation beyond simply angiogenesis. To elucidate whether VEGFR-2 activation plays a role in hair follicle cycling regulation, immunofluorescence of VEGFR-2 expression was performed during hair cycling of the dorsum of the mouse induced by hair plucking. We observed that staining for VEGFR-2 in hair follicles during anagen II and IV was much stronger than during anagen VI, catagen and telogen. During anagen II, intense staining for VEGFR-2 was observed on the keratinocyte strands of the hair follicle. Subsequently, we detected intense staining for VEGFR-2 in the ORS, IRS and hair bulb during anagen IV. Moderate staining for VEGFR-2 was detected in the ORS and hair bulb, but staining was most intense in IRS during anagen VI. During catagen, staining for VEGFR-2 in the IRS remained intense, while staining in the ORS and hair bulb was significantly weakened and was negative in the dermal papilla. During telogen, we detected VEGFR-2 in germ cells, cap, and club hair adjoining the epidermis. In conclusion, VEGFR-2 was expressed on the hair follicles of the dorsum of the mouse and varied in expression on the mouse hair follicles during hair cycling, suggesting that VEGFR-2 may exert roles in hair cycle regulation in hair follicles on the dorsum of mice.

Effect of helium-neon laser irradiation on hair follicle growth cycle of Swiss albino mice.

PubMed

Shukla, S; Sahu, K; Verma, Y; Rao, K D; Dube, A; Gupta, P K

2010-01-01

We report the results of a study carried out to investigate the effect of helium-neon (He-Ne) laser (632.8 nm) irradiation on the hair follicle growth cycle of testosterone-treated and untreated mice. Both histology and optical coherence tomography (OCT) were used for the measurement of hair follicle length and the relative percentage of hair follicles in different growth phases. A positive correlation (R = 0.96) was observed for the lengths of hair follicles measured by both methods. Further, the ratios of the lengths of hair follicles in the anagen and catagen phases obtained by both methods were nearly the same. However, the length of the hair follicles measured by both methods differed by a factor of 1.6, with histology showing smaller lengths. He-Ne laser irradiation (at approximately 1 J/cm(2)) of the skin of both the control and the testosterone-treated mice was observed to lead to a significant increase (p < 0.05) in % anagen, indicating stimulation of hair growth. The study also demonstrates that OCT can be used to monitor the hair follicle growth cycle, and thus hair follicle disorders or treatment efficacy during alopecia. (c) 2009 S. Karger AG, Basel.

Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage.

PubMed

Arck, Petra Clara; Overall, Rupert; Spatz, Katharina; Liezman, Christiane; Handjiski, Bori; Klapp, Burghard F; Birch-Machin, Mark A; Peters, Eva Milena Johanne

2006-07-01

Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.

Melatonin promotes Cashmere goat (Capra hircus) secondary hair follicle growth: A view from integrated analysis of long non-coding and coding RNAs.

PubMed

Ge, Wei; Wang, Shan-He; Sun, Bing; Zhang, Yue-Lang; Shen, Wei; Khatib, Hasan; Wang, Xin

2018-06-12

The role of melatonin in promoting the yield of Cashmere goat wool has been demonstrated for decades though there remains a lack of knowledge regarding melatonin mediated hair follicle growth. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are widely transcribed in the genome and play ubiquitous roles in regulating biological processes. However, the role of lncRNAs in regulating melatonin mediated hair follicle growth remains unclear. In this study, we established an in vitro Cashmere goat secondary hair follicle culture system, and demonstrated that 500 ng/L melatonin exposure promoted hair follicle fiber growth. Based on long intergenic RNA sequencing, we demonstrated that melatonin promoted hair follicle elongation via regulating genes involved in focal adhesion and extracellular matrix receptor pathways and further cis predicting of lncRNAs targeted genes indicated that melatonin mediated lncRNAs mainly targeted vascular smooth muscle contraction and signaling pathways regulating the pluripotency of stem cells. We proposed that melatonin exposure not only perturbed key signals secreted from hair follicle stem cells to regulate hair follicle development, but also mediated lncRNAs mainly targeted to pathways involved in the microvascular system and extracellular matrix, which constitute the highly orchestrated microenvironment for hair follicle stem cell. Taken together, our findings here provide a profound view of lncRNAs in regulating Cashmere goat hair follicle circadian rhythms and broaden our knowledge on melatonin mediated hair follicle morphological changes.

Reflectance spectroscopy for noninvasive evaluation of hair follicle stage

NASA Astrophysics Data System (ADS)

Liu, Caihua; Guan, Yue; Wang, Jianru; Zhong, Xiewei; Liu, Xiuli; Zhu, Dan

2015-05-01

Hair follicle offers an excellent model for systems biology and regenerative medicine. So far, the stages of hair follicle growth have been evaluated by histological examination. In this work, a noninvasive spectroscopy was proposed by measuring the diffuse reflectance of mouse skin and analyzing the melanin value. Results show that the skin diffuse reflectance was relatively high when hair follicles were at the telogen stage and at the beginning of the anagen stage, and decreased with the progression of the anagen stage. When the hair follicle entered into the catagen stage, the diffuse reflectance gradually increased. The changes in the melanin content of skin had contrary dynamics. Substages of the hair follicle cycle could be distinguished by comparing the changes in melanin value with the histological examination. This study provided a new method for noninvasive evaluation of the hair follicle stage, and should be valuable for basic and therapeutic investigations on hair regeneration.

Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy.

PubMed

Sharova, Tatyana Y; Poterlowicz, Krzysztof; Botchkareva, Natalia V; Kondratiev, Nikita A; Aziz, Ahmar; Spiegel, Jeffrey H; Botchkarev, Vladimir A; Sharov, Andrey A

2014-12-01

Chemotherapy has severe side effects in normal rapidly proliferating organs, such as hair follicles, and causes massive apoptosis in hair matrix keratinocytes followed by hair loss. To define the molecular signature of hair follicle response to chemotherapy, human scalp hair follicles cultured ex vivo were treated with doxorubicin (DXR), and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in DXR-treated hair follicles versus controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptors 1/2), as well as of a large number of keratin-associated protein genes, were seen after DXR treatment. Hair follicle apoptosis induced by DXR was significantly inhibited by either TRAIL-neutralizing antibody or caspase-8 inhibitor, thus suggesting a previously unreported role for TRAIL receptor signaling in mediating DXR-induced hair loss. These data demonstrate that the early phase of the hair follicle response to DXR includes upregulation of apoptosis-associated markers, as well as substantial reorganization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies toward the design of effective approaches for the management of chemotherapy-induced hair loss.

Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy

PubMed Central

Sharova, Tatyana Y.; Poterlowicz, Krzysztof; Botchkareva, Natalia V.; Kondratiev, Nikita A.; Aziz, Ahmar; Spiegel, Jeffrey H.; Botchkarev, Vladimir A.; Sharov, Andrey A.

2014-01-01

Chemotherapy has severe side-effects for normal rapidly proliferating organs, such as hair follicle, and causes massive apoptosis in hair matrix keratinocytes followed by hair loss. To define the molecular signature of hair follicle response to chemotherapy, human scalp hair follicles cultured ex vivo were treated with doxorubicin and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in doxorubicin-treated hair follicles versus the controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL receptors 1/2), as well as of a large number of the keratin-associated protein genes were seen after doxorubicin treatment. Hair follicle apoptosis induced by doxorubicin was significantly inhibited by either TRAIL neutralizing antibody or caspase 8 inhibitor, thus suggesting a novel role for TRAIL receptor signaling in mediating doxorubicin-induced hair loss. These data demonstrate that the early phase of the hair follicle response to doxorubicin includes upregulation of apoptosis-associated markers, as well as substantial re-organization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies towards the design of novel approaches for management of chemotherapy-induced hair loss. PMID:24999588

The hair follicle enigma.

PubMed

Bernard, Bruno A

2017-06-01

The hair follicle is a mini-organ endowed with a unique structure and cyclic behaviour. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome-mediated cell-cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Functional Role of RB-Dependent Pathway in the Control of Quiescence in Adult Epidermal Stem Cells Revealed by Genomic Profiling

PubMed Central

Lorz, Corina; García-Escudero, Ramón; Segrelles, Carmen; Garín, Marina I.; Ariza, José M.; Santos, Mirentxu; Ruiz, Sergio; Lara, María F.; Martínez-Cruz, Ana B.; Costa, Clotilde; Buitrago-Pérez, Águeda; Saiz-Ladera, Cristina; Dueñas, Marta

2010-01-01

Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis. Electronic supplementary material The online version of this article (doi:10.1007/s12015-010-9139-0) contains supplementary material, which is available to authorized users. PMID:20376578

KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin

PubMed Central

Richardson, Gavin D.; Bazzi, Hisham; Fantauzzo, Katherine A.; Waters, James M.; Crawford, Heather; Hynd, Phil; Christiano, Angela M.; Jahoda, Colin A. B.

2009-01-01

Summary A key initial event in hair follicle morphogenesis is the localised thickening of the skin epithelium to form a placode, partitioning future hair follicle epithelium from interfollicular epidermis. Although many developmental signalling pathways are implicated in follicle morphogenesis, the role of epidermal growth factor (EGF) and keratinocyte growth factor (KGF, also known as FGF7) receptors are not defined. EGF receptor (EGFR) ligands have previously been shown to inhibit developing hair follicles; however, the underlying mechanisms have not been characterised. Here we show that receptors for EGF and KGF undergo marked downregulation in hair follicle placodes from multiple body sites, whereas the expression of endogenous ligands persist throughout hair follicle initiation. Using embryonic skin organ culture, we show that when skin from the sites of primary pelage and whisker follicle development is exposed to increased levels of two ectopic EGFR ligands (HBEGF and amphiregulin) and the FGFR2(IIIb) receptor ligand KGF, follicle formation is inhibited in a time- and dose-dependent manner. We then used downstream molecular markers and microarray profiling to provide evidence that, in response to KGF and EGF signalling, epidermal differentiation is promoted at the expense of hair follicle fate. We propose that hair follicle initiation in placodes requires downregulation of the two pathways in question, both of which are crucial for the ongoing development of the interfollicular epidermis. We have also uncovered a previously unrecognised role for KGF signalling in the formation of hair follicles in the mouse. PMID:19474150

Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells

NASA Astrophysics Data System (ADS)

Yang, Ruifeng; Zheng, Ying; Burrows, Michelle; Liu, Shujing; Wei, Zhi; Nace, Arben; Guo, Wei; Kumar, Suresh; Cotsarelis, George; Xu, Xiaowei

2014-01-01

Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200+/ITGA6+ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200+/ITGA6+ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200+/ITGA6+ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15+ stem cell population and produce hair shafts expressing hair-specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.

Analysis of the penetration of a caffeine containing shampoo into the hair follicles by in vivo laser scanning microscopy

NASA Astrophysics Data System (ADS)

Lademann, J.; Richter, H.; Schanzer, S.; Klenk, A.; Sterry, W.; Patzelt, A.

2010-02-01

In previous in vitro investigations, it was demonstrated that caffeine is able to stimulate the hair growth. Therefore, a penetration of caffeine into the hair follicle is necessary. In the present study, in vivo laser scanning microscopy (LSM) was used to investigate the penetration and storage of a caffeine containing shampoo into the hair follicles. It was shown that a 2-min contact time of the shampoo with the skin was enough to accumulate significant parts of the shampoo in the hair follicles. A penetration of the shampoo up to a depth of approx. 200 μm could be detected, which represents the detection limit of the LSM. At this depth, the close network of the blood capillaries surrounding the hair follicles commences. Even after 24 h, the substance was still detectable in the hair follicles. This demonstrates the long-term reservoir function of the hair follicles for topically applied substances such as caffeine.

Wnt/β-catenin signaling in dermal condensates is required for hair follicle formation

PubMed Central

Tsai, Su-Yi; Sennett, Rachel; Rezza, Amélie; Clavel, Carlos; Grisanti, Laura; Zemla, Roland; Najam, Sara; Rendl, Michael

2014-01-01

Broad dermal Wnt signaling is required for patterned induction of hair follicle placodes and subsequent Wnt signaling in placode stem cells is essential for induction of dermal condensates, cell clusters of precursors for the hair follicle dermal papilla (DP). Progression of hair follicle formation then requires coordinated signal exchange between dermal condensates and placode stem cells. However, it remains unknown whether continued Wnt signaling in DP precursor cells plays a role in this process, largely due to the long-standing inability to specifically target dermal condensates for gene ablation. Here we use the Tbx18Cre knockin mouse line to ablate the Wnt-responsive transcription factor β-catenin specifically in these cells at E14.5 during the first wave of guard hair follicle formation. In the absence of β-catenin, canonical Wnt signaling is effectively abolished in these cells. Sox2+ dermal condensates initiate normally, however by E16.5 guard hair follicle numbers are strongly reduced and by E18.5 most whiskers and guard hair follicles are absent, suggesting that active Wnt signaling in dermal condensates is important for hair follicle formation to proceed after induction. To explore the molecular mechanisms by which Wnt signaling in dermal condensates regulates hair follicle formation, we analyze genome-wide the gene expression changes in embryonic β-catenin null DP precursor cells. We find altered expression of several signaling pathway genes, including Fgfs and Activin, both previously implicated in hair follicle formation. In summary, these data reveal a functional role of Wnt signaling in DP precursors for embryonic hair follicle formation and identify Fgf and Activin signaling as potential effectors of Wnt signaling-regulated events. PMID:24309208

Effects of gamma rays on the regeneration of murine hair follicles in the natural hair cycle.

PubMed

Sugaya, Kimihiko

2017-09-01

This review evaluates the effects of γ-rays on the regeneration of murine hair follicles in the natural hair cycle. A series of studies were performed to investigate this issue, in which the whole bodies of C57BL/10JHir mice in the 1st telogen phase of the hair cycle were irradiated with γ-rays. The dermis of the irradiated skin showed a decrease in hair follicle density and induction of curved hair follicles along with the presence of white hairs and hypopigmented hair bulbs in the 2nd and 3rd anagen phases. An increased frequency of hypopigmented hair bulbs was still observed in the later hair cycle at postnatal day 200. There was no significant difference in the number of stem cells in the hair bulge region between control and irradiated skin. These results show that the effects of γ-rays on the pigmentation of murine hair follicles are persistently carried over to later hair cycles, although those on the number and structure of hair follicles appear to be hidden by the effects of aging. Our findings may be important for understanding the mechanisms of the actions of stem cells on hair regeneration in connection with age-related phenotypes.

Canonical and non-canonical Wnt signaling control the regeneration of amputated rodent vibrissae follicles.

PubMed

Yuan, Yan-Ping; Huang, Keng; Xu, Yan-Min; Chen, Xian-Cai; Li, Hai-Hong; Cai, Bo-Zhi; Liu, Yang; Zhang, Huan; Li, Yu; Lin, Chang-Min

2016-02-01

Although mammals are notoriously poor at regeneration compared with many lower-order species, the hair follicle, particular to mammals, is capable of regeneration following partial amputation. The detailed internal mechanism of this phenomenon is still unclear. Development and regrowth of the hair follicle depends on dermal-epidermal interaction within the hair follicle. Previous studies have shown that Wnt/β-catenin, Shh, Bmp, PDGF, TGF and Notch signals all take part in the development and growth of the hair follicle, and the Wnt/β-catenin signaling additionally plays an indispensable role in hair follicle morphogenesis and regrowth. In this study, we investigated the localization, as well as, protein levels of Wnt/β-catenin signaling molecules during amputated whisker follicle regeneration.

Hair Follicle Nevus With Features of Comedo Nevus: An Expanding Spectrum.

PubMed

Nagarajan, Priyadharsini; Bartholomew, Timothy S; Allen, Carl M; Peters, Sara B

2016-06-01

Hair follicle nevus (HFN) is a rare hamartomatous lesion of the folliculosebaceous unit, with or without admixed fibroadipose or muscular tissue. It typically has a congenital presentation in the preauricular area of infants and is frequently confused with an accessory tragus. Acquired tumors with similar histopathologic features have been described infrequently during adolescence and adult life. We report yet another unique presentation of this unusual lesion in a 4-year-old girl who had a long-standing tumor of the nasal columella that started growing rapidly after trauma. Histopathologic examination revealed increased numbers of hair follicles, some of which were associated with diminutive sebaceous glands, with no associated central cystic structure. In addition, the infundibula of the follicles were dilated and filled with keratinous debris. Although these hamartomas are common in the head and neck region, to our knowledge, this is the first report of a HFN at this anatomic location. In addition, this tumor has an overall architecture of a HFN but is accompanied by features of a comedo nevus. We also present a review of the literature and summarize the current diagnostic criteria for HFN.

Expression and function of glycogen synthase kinase-3 in human hair follicles.

PubMed

Yamauchi, Koichi; Kurosaka, Akira

2010-05-01

Beta-catenin is involved in the hair follicle morphogenesis and stem cell differentiation, and inhibition of glycogen synthase kinase-3 (GSK-3) increases beta-catenin concentration in the cytoplasm. To examine the effects of GSK-3 inhibition on the hair follicle epithelium, we first examined the expression of GSK-3 in plucked human hair follicles by RT-PCR and found GSK-3 expression in hair follicles. Western blotting with a GSK-3beta-specific antibody, Y174, also demonstrated GSK-3beta expression in the follicles. Moreover, GSK-3beta immunostaining with Y174 showed that GSK-3beta colocalized with hair follicle bulge markers. Contrary to GSK-3beta, GSK-3 alpha was widely expressed throughout the follicles when immunostained with a specific antibody, EP793Y. We then investigated the influence of GSK-3 inhibition. A GSK-3 inhibitor, BIO, promoted the growth of human outer root sheath cells, which could be cultured for up to four passages. The BIO-treated cells exhibited smaller and more undifferentiated morphology than control cells. Moreover, in organ culture of plucked human hair, outer root sheath cells in the middle of a hair follicle proliferated when cultured with BIO. These results indicate that GSK-3beta is expressed in hair bulge stem cells and BIO promotes the growth of ORS cells, possibly by regulating the GSK-3 signaling pathway.

Three different clinical faces of the same histopathological entity: hair follicle nevus, trichofolliculoma and accessory tragus*

PubMed Central

Karabulut, Yasemin Yuyucu; Şenel, Engin; Karabulut, Hacı Halil; Dölek, Yasemin

2015-01-01

BACKGROUND Hair follicle nevus is a rare, congenital hamartoma with follicular differentiation characterized histologically by numerous, tiny, mature hair follicles. Trichofolliculoma, the histopathological features of which are quite similar to those of hair follicle nevus, is also a hamartoma that differs from hair follicle. Accessory tragus is a relatively common, benign congenital abnormality of the external ear with an incidence rate of 1 to 10 per 1,000 live births. OBJECTIVE This study seeks to assess the discriminatory value of currently available, histological criteria in the differential diagnosis of hair follicle nevus, accessory tragi and trichofolliculoma. METHODS Twenty-one patients comprising 9 cases of hair follicle nevus, 8 accessory tragi patients and 4 trichofolliculoma cases, were recruited to perform the study. RESULTS There were 10 males and 11 females in the study group. No significant difference was observed between the three study groups in terms of age, gender or histopathological parameters such as density of hair follicles, subcutaneous fat score and presence of connective tissue framework. Cartilaginous component was seen in 8 cases that were diagnosed as accessory tragi, while central cyst and radiating hair follicles were seen in 4 cases which were diagnosed as trichofolliculoma. CONCLUSION The results of our study showed that diagnostic discrimination of these diseases could be made only with the clinicopathologic correlation because of their clinical and histopathological similarities. PMID:26375221

Three different clinical faces of the same histopathological entity: hair follicle nevus, trichofolliculoma and accessory tragus.

PubMed

Karabulut, Yasemin Yuyucu; Şenel, Engin; Karabulut, Hacı Halil; Dölek, Yasemin

2015-01-01

Hair follicle nevus is a rare, congenital hamartoma with follicular differentiation characterized histologically by numerous, tiny, mature hair follicles. Trichofolliculoma, the histopathological features of which are quite similar to those of hair follicle nevus, is also a hamartoma that differs from hair follicle. Accessory tragus is a relatively common, benign congenital abnormality of the external ear with an incidence rate of 1 to 10 per 1,000 live births. This study seeks to assess the discriminatory value of currently available, histological criteria in the differential diagnosis of hair follicle nevus, accessory tragi and trichofolliculoma. Twenty-one patients comprising 9 cases of hair follicle nevus, 8 accessory tragi patients and 4 trichofolliculoma cases, were recruited to perform the study. There were 10 males and 11 females in the study group. No significant difference was observed between the three study groups in terms of age, gender or histopathological parameters such as density of hair follicles, subcutaneous fat score and presence of connective tissue framework. Cartilaginous component was seen in 8 cases that were diagnosed as accessory tragi, while central cyst and radiating hair follicles were seen in 4 cases which were diagnosed as trichofolliculoma. The results of our study showed that diagnostic discrimination of these diseases could be made only with the clinicopathologic correlation because of their clinical and histopathological similarities.

Expression and distribution patterns of spermine, spermidine, and putrescine in rat hair follicle.

PubMed

Yamamoto, Yutaro; Makino, Takamitsu; Kudo, Hideo; Ihn, Hironobu; Murakami, Yasuko; Matsufuji, Senya; Fujiwara, Kunio; Shin, Masashi

2018-02-01

No expression and distribution patterns of polyamines (PAs), spermine, spermidine, and their precursor putrescine in mammalian hair follicle are available, although polyamines are known to correlate well with hair growth and epidermal tumor genesis. Immunohistochemistry (IHC) using our original two monoclonal antibodies (mAbs) ASPM-29 specific for spermine or spermidine, and APUT-32 specific for putrescine allowed us to detect immunoreactivity for polyamines in hair follicles from normal adult rats. A wide range of immunoreactivity for the total spermine and spermidine was observed in the compartments of hair follicle: The highest degree of immunoreactivity for polyamines was observed in the matrix, in the Huxley's layer, in the deeper Henle's layer, and in the cuticle of the inner root sheath/the hair cuticle, while moderate immunoreactivity existed in the lower-to-mid cortex and the companion layer, followed by lower immunoreactivity in the outer root sheath, including the bulge region and in the deeper medulla, in which the immunoreactivity was also evident in their nuclei. In addition, somewhat surprisingly, with IHC by APUT-32 mAb, we detected significant levels of putrescine in the compartments, in which the immunostaining pattern was the closely similar to that of the total spermine and spermidine. Thus, among these compartments, the cell types of the matrix, the Huxley's layer, the deeper Henle's layer, and the cuticle of the inner root sheath/the hair cuticle seem to have the biologically higher potential in compartments of anagen hair follicle, maybe suggesting that they are involved more critically in the biological event of hair growth. In addition, we noted sharp differences of immunostaining by IHCs between ASPM-29 mAb and APUT-32 mAb in the epidermis cells and fibroblast. ASPM-29 mAb resulted in strong staining in both the cell types, but APUT-32 mAb showed only very light staining in both types. Consequently, the use of the two IHCs could be extremely useful in further studies on hair cycle and epidermal tumor genesis experimentally or clinically.

ILK modulates epithelial polarity and matrix formation in hair follicles.

PubMed

Rudkouskaya, Alena; Welch, Ian; Dagnino, Lina

2014-03-01

Hair follicle morphogenesis requires coordination of multiple signals and communication between its epithelial and mesenchymal constituents. Cell adhesion protein platforms, which include integrins and integrin-linked kinase (ILK), are critical for hair follicle formation. However, their precise contribution to this process is poorly understood. We show that in the absence of ILK, the hair follicle matrix lineage fails to develop, likely due to abnormalities in development of apical-basal cell polarity, as well as in laminin-511 and basement membrane assembly at the tip of the hair bud. These defects also result in impaired specification of hair matrix and absence of precortex and inner sheath root cell lineages. The molecular pathways affected in ILK-deficient follicles are similar to those in the absence of epidermal integrin β1 and include Wnt, but not sonic hedgehog, signaling. ILK-deficient hair buds also show abnormalities in the dermal papilla. Addition of exogenous laminin-511 restores morphological and molecular markers associated with hair matrix formation, indicating that ILK regulates hair bud cell polarity and functions upstream from laminin-511 assembly to regulate the developmental progression of hair follicles beyond the germ stage.

Regeneration of Murine Hair Follicles is Inhibited by Low-Dose-Rate Gamma Irradiation.

PubMed

Sugaya, Kimihiko; Hirobe, Tomohisa; Ishihara, Yoshie; Inoue, Sonoe

2016-10-01

To determine whether the effects of low-dose-rate gamma (γ) irradiation are identifiable in the regeneration of murine hair follicles, we irradiated whole bodies of C57BL/10JHir mice in the first telogen phase of the hair cycle with 137 Cs γ-rays. The mice were examined for effects on hair follicles, including number, morphology, and pigmentation in the second anagen phase. Effects of γ-radiation on melanocyte stem cells were also investigated by the indirect immunolabeling of tyrosinase-related protein 2 (TRP2). Irradiated skin showed a decrease in hair follicle density and the induction of curved hair follicles along with the presence of white hairs and hypopigmented hair bulbs. There was a small, but not significant, change in the number of TRP2-positive melanocyte stem cells in the hair bulge region of the irradiated skin. These results suggest that low-dose rate γ-irradiation does not deplete melanocyte stem cells, but can damage stem cells and progenitors for both keratinocytes and melanocytes, thereby affecting the structure and pigmentation of regenerated hair follicles in the 2 nd anagen phase.

A new path in defining light parameters for hair growth: Discovery and modulation of photoreceptors in human hair follicle.

PubMed

Buscone, Serena; Mardaryev, Andrei N; Raafs, Bianca; Bikker, Jan W; Sticht, Carsten; Gretz, Norbert; Farjo, Nilofer; Uzunbajakava, Natallia E; Botchkareva, Natalia V

2017-09-01

Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light-sensitive receptors in the human hair follicle and to study the impact of UV-free blue light on hair growth ex vivo. The expression of Opsin receptors in human skin and hair follicles has been characterized using RT-qPCR and immunofluorescence approaches. The functional significance of Opsin 3 was assessed by silencing its expression in the hair follicle cells followed by a transcriptomic profiling. Proprietary LED-based devices emitting two discrete visible wavelengths were used to access the effects of selected optical parameters on hair growth ex vivo and outer root sheath cells in vitro. The expression of OPN2 (Rhodopsin) and OPN3 (Panopsin, Encephalopsin) was detected in the distinct compartments of skin and anagen hair follicle. Treatment with 3.2 J/cm 2 of blue light with 453 nm central wavelength significantly prolonged anagen phase in hair follicles ex vivo that was correlated with sustained proliferation in the light-treated samples. In contrast, hair follicle treatment with 3.2 J/cm 2 of 689 nm light (red light) did not significantly affect hair growth ex vivo. Silencing of OPN3 in the hair follicle outer root sheath cells resulted in the altered expression of genes involved in the control of proliferation and apoptosis, and abrogated stimulatory effects of blue light (3.2 J/cm 2 ; 453 nm) on proliferation in the outer root sheath cells. We provide the first evidence that (i) OPN2 and OPN3 are expressed in human hair follicle, and (ii) A 453 nm blue light at low radiant exposure exerts a positive effect on hair growth ex vivo, potentially via interaction with OPN3. Lasers Surg. Med. 49:705-718, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station

PubMed Central

Terada, Masahiro; Seki, Masaya; Takahashi, Rika; Yamada, Shin; Higashibata, Akira; Majima, Hideyuki J.; Sudoh, Masamichi; Mukai, Chiaki; Ishioka, Noriaki

2016-01-01

Adaptation to the space environment can sometimes pose physiological problems to International Space Station (ISS) astronauts after their return to earth. Therefore, it is important to develop healthcare technologies for astronauts. In this study, we examined the feasibility of using hair follicles, a readily obtained sample, to assess gene expression changes in response to spaceflight adaptation. In order to investigate the gene expression changes in human hair follicles during spaceflight, hair follicles of 10 astronauts were analyzed by microarray and real time qPCR analyses. We found that spaceflight alters human hair follicle gene expression. The degree of changes in gene expression was found to vary among individuals. In some astronauts, genes related to hair growth such as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that spaceflight inhibits cell proliferation in hair follicles. PMID:27029003

Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station.

PubMed

Terada, Masahiro; Seki, Masaya; Takahashi, Rika; Yamada, Shin; Higashibata, Akira; Majima, Hideyuki J; Sudoh, Masamichi; Mukai, Chiaki; Ishioka, Noriaki

2016-01-01

Adaptation to the space environment can sometimes pose physiological problems to International Space Station (ISS) astronauts after their return to earth. Therefore, it is important to develop healthcare technologies for astronauts. In this study, we examined the feasibility of using hair follicles, a readily obtained sample, to assess gene expression changes in response to spaceflight adaptation. In order to investigate the gene expression changes in human hair follicles during spaceflight, hair follicles of 10 astronauts were analyzed by microarray and real time qPCR analyses. We found that spaceflight alters human hair follicle gene expression. The degree of changes in gene expression was found to vary among individuals. In some astronauts, genes related to hair growth such as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that spaceflight inhibits cell proliferation in hair follicles.

Exogenous IGF-1 promotes hair growth by stimulating cell proliferation and down regulating TGF-β1 in C57BL/6 mice in vivo.

PubMed

Li, Jingjie; Yang, Zhihong; Li, Zheng; Gu, Lijuan; Wang, Yunbo; Sung, Changkeun

2014-01-01

Insulin-like growth factor 1 (IGF-1) increases the growth of cultured hair follicles and plays a role in regulating hair migration during the development of hair follicles in transgenic mice. However, the exogenous effect of IGF-1 on hair growth in wild-type mice has not been reported. In the present study, we examined whether IGF-1 was an important regulator of hair follicle growth in wide-type mice in vivo. C57BL/6 mice were injected with different concentrations of IGF-1 on dorsal skin. The treated tissues were analyzed by immunoassay methods for TGF-β1 and BrdU. Local injection of IGF-1 increased hair follicle number and prolonged the growing phase during the transition from anagen to telogen. Meanwhile, immunology analyses revealed that IGF-1 also stimulated the proliferation of follicle cells in anagen of the matrix and down regulated TGF-β1 expression in hair follicles. These observations suggest that IGF-1 is an effective stimulator of hair follicle development in wide-type mice in vivo and may be a promising drug candidate for baldness therapy. Copyright © 2014. Published by Elsevier Ltd.

Hair organ regeneration via the bioengineered hair follicular unit transplantation

PubMed Central

Asakawa, Kyosuke; Toyoshima, Koh-ei; Ishibashi, Naoko; Tobe, Hirofumi; Iwadate, Ayako; Kanayama, Tatsuya; Hasegawa, Tomoko; Nakao, Kazuhisa; Toki, Hiroshi; Noguchi, Shotaro; Ogawa, Miho; Sato, Akio; Tsuji, Takashi

2012-01-01

Organ regenerative therapy aims to reproduce fully functional organs to replace organs that have been lost or damaged as a result of disease, injury, or aging. For the fully functional regeneration of ectodermal organs, a concept has been proposed in which a bioengineered organ is developed by reproducing the embryonic processes of organogenesis. Here, we show that a bioengineered hair follicle germ, which was reconstituted with embryonic skin-derived epithelial and mesenchymal cells and ectopically transplanted, was able to develop histologically correct hair follicles. The bioengineered hair follicles properly connected to the host skin epithelium by intracutaneous transplantation and reproduced the stem cell niche and hair cycles. The bioengineered hair follicles also autonomously connected with nerves and the arrector pili muscle at the permanent region and exhibited piloerection ability. Our findings indicate that the bioengineered hair follicles could restore physiological hair functions and could be applicable to surgical treatments for alopecia. PMID:22645640

Comparison of hair follicle histology between horses with pituitary pars intermedia dysfunction and excessive hair growth and normal aged horses.

PubMed

Innerå, Marie; Petersen, Annette D; Desjardins, Danielle R; Steficek, Barbara A; Rosser, Edmund J; Schott, Harold C

2013-02-01

Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed. The aim of this study was to compare hair follicle stages in PPID-affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID-affected horses after 6 months of treatment with pergolide mesylate with those of control horses. Eight PPID-affected horses and four normal, age-matched, control horses. Skin biopsies were collected from the neck and rump of PPID-affected and control horses. A diagnosis of PPID was established based on hair coat changes and supportive overnight dexamethasone suppression test results. Skin biopsies were repeated after 6 months of treatment with pergolide. The number of hair follicles in anagen (A) or telogen (T) was counted for each skin biopsy using transverse sections. Pretreatment biopsies had a greater percentage of A follicles (neck 96%, rump 95%) and a lower percentage of T follicles (neck 4%, rump 5%) in PPID-affected horses than in control horses (A, neck 15%, rump 25%; and T, neck 85%, rump 75%). After treatment with pergolide, all PPID-affected horses had improved shedding, and the percentages of A follicles (neck 69%, rump 70%) and T follicles (neck 31%, rump 30%) were not different from untreated control horses (A, neck 68%, rump 82%; and T, neck 32%, rump 18%). These findings document that excessive hair growth (hypertrichosis) in PPID-affected horses is due to persistence of hair follicles in A. Furthermore, treatment with pergolide improved shedding and reduced the percentage of A follicles in PPID-affected horses. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

[Technologies for hair reconstruction and their applicability for pharmaceutical research].

PubMed

Matsuzaki, Takashi

2008-01-01

Hair follicles are the organs that produce hair shafts. They periodically regenerate throughout the life of the organisms, which is called the hair cycle. To develop new drugs to treat hair disorders and diseases, reproducible and high throughput assays or screening methods have been required to estimate the efficacy of various factors on hair follicle function. Although organ culture of hair follicles is one of the useful ways to carry out such research, it is not suitable for manipulating the genes or cells present in hair follicles. Patch assay is a method used to reconstruct hair follicles from enzymatically dissociated skin cells and has many advantages compared to the conventional Chamber method. Using the Patch method, transferring genes into follicular cells becomes easier than ever before. Chimeric follicles could be produced with dissociated cells by modifying the combination of cells or by simply merging cells of different origins. These applications certainly help the progress of hair research. However, we recently found that some functions of dermal papillae and follicular epithelia change during the growing phase (anagen) of the hair cycle. Dermal papillae produce different factors in early anagen and mid anagen. The signals from dermal papillae in early anagen could produce hair bulbs with clonogenic epithelial precursors but not with dormant epithelial precursors. On the other hand, the signals from dermal papillae in mid anagen strongly promote hair formation with dormant epithelial precursors. Therefore, more attention should be given to the hair cycle stages when using organ culture of hair follicles and conducting reconstruction experiments with follicularly derived cells.

The importance of basonuclin 2 in adult mice and its relation to basonuclin 1.

PubMed

Vanhoutteghem, Amandine; Delhomme, Brigitte; Hervé, Françoise; Nondier, Isabelle; Petit, Jean-Maurice; Araki, Masatake; Araki, Kimi; Djian, Philippe

2016-05-01

BNC2 is an extremely conserved zinc finger protein with important functions in the development of craniofacial bones and male germ cells. Because disruption of the Bnc2 gene in mice causes neonatal lethality, the function of the protein in adult animals has not been studied. Until now BNC2 was considered to have a wider tissue distribution than its paralog, BNC1, but the precise cell types expressing Bnc2 are largely unknown. We identify here the cell types containing BNC2 in the mouse and we show the unexpected presence of BNC1 in many BNC2-containing cells. BNC1 and BNC2 are colocalized in male and female germ cells, ovarian epithelial cells, sensory neurons, hair follicle keratinocytes and connective cells of organ capsules. In many cell lineages, the two basonuclins appear and disappear synchronously. Within the male germ cell lineage, BNC1 and BNC2 are found in prospermatogonia and undifferentiated spermatogonia, and disappear abruptly from differentiating spermatogonia. During oogenesis, the two basonuclins accumulate specifically in maturing oocytes. During the development of hair follicles, BNC1 and BNC2 concentrate in the primary hair germs. As follicle morphogenesis proceeds, cells possessing BNC1 and BNC2 invade the dermis and surround the papilla. During anagen, BNC1 and BNC2 are largely restricted to the basal layer of the outer root sheath and the matrix. During catagen, the compartment of cells possessing BNC1 and BNC2 regresses, and in telogen, the two basonuclins are confined to the secondary hair germ. During the next anagen, the BNC1/BNC2-containing cell population regenerates the hair follicle. By examining Bnc2(-/-) mice that have escaped the neonatal lethality usually associated with lack of BNC2, we demonstrate that BNC2 possesses important functions in many of the cell types where it resides. Hair follicles of postnatal Bnc2(-/-) mice do not fully develop during the first cycle and thereafter remain blocked in telogen. It is concluded that the presence of BNC2 in the secondary hair germ is required to regenerate the transient segment of the follicle. Postnatal Bnc2(-/-) mice also show severe dwarfism, defects in oogenesis and alterations of palatal rugae. Although the two basonuclins possess very similar zinc fingers and are largely coexpressed, BNC1 cannot substitute for BNC2. This is shown incontrovertibly in knockin mice expressing Bnc1 instead of Bnc2 as these mice invariably die at birth with craniofacial abnormalities undistinguishable from those of Bnc2(-/-) mice. The function of the basonuclins in the secondary hair germ is of particular interest. Copyright © 2016 Elsevier B.V. All rights reserved.

Multiple roles for elastic fibers in the skin.

PubMed

Starcher, Barry; Aycock, Ronnie L; Hill, Charles H

2005-04-01

Dermal elastic fibers are believed to have a primary role in providing elastic stretch and recoil to the skin. Here we compare the structural arrangement of dermal elastic fibers of chick skin and different animal species. Most elastic fibers in chick skin are derived from cells that line the feather follicle and/or smooth muscle that connects the pterial and apterial muscle bundles to feather follicles. Elastic fibers in the dermis of animals with single, primary hair follicles are derived from cells lining the hair follicle or from the ends of the pili muscle, which anchors the muscle to the matrix or to the hair follicle. Each follicle is interconnected with elastic fibers. Follicles of animals with primary and secondary (wool) hair follicles are also interconnected by elastic fibers, yet only the elastic fibers derived from the primary follicle are connected to each primary follicle. Only the primary hair follicles are connected to the pili muscle. Human skin, but not the skin of other primates, is significantly different from other animals with respect to elastic fiber organization and probably cell of origin. The data suggest that the primary role for elastic fibers in animals, with the possible exception of humans, is movement and/or placement of feathers or hair.

Hair follicle nevus - A dermoscopic approach.

PubMed

Okada, Junna; Moroi, Yoichi; Tsujita, Jun; Takahara, Masakazu; Urabe, Kazunori; Kiryu, Hiromaro; Furue, Masutaka

2008-01-01

We report the case of a 26-year-old man who presented with small soft nodules with tiny hairs that had been present on his nose since childhood. The nodules were initially diagnosed as melanocytic nevi. However, dermoscopy showed many uniform hair follicles and an interfollicular 'pseudo-pigment network' in the nodules. Histologically, many well-differentiated hair follicles and sebaceous glands were seen in the dermis. Serial sectioning revealed neither central cysts nor a central canal. We therefore diagnosed this case as hair follicle nevus. Dermoscopy is now widely used as a non-invasive, in vivo technique for the diagnosis of pigmented skin lesions. Hair follicle nevus is a very rare disease and this is the first report to demonstrate the manifestation of this clinical entity by dermoscopy.

ILK modulates epithelial polarity and matrix formation in hair follicles

PubMed Central

Rudkouskaya, Alena; Welch, Ian; Dagnino, Lina

2014-01-01

Hair follicle morphogenesis requires coordination of multiple signals and communication between its epithelial and mesenchymal constituents. Cell adhesion protein platforms, which include integrins and integrin-linked kinase (ILK), are critical for hair follicle formation. However, their precise contribution to this process is poorly understood. We show that in the absence of ILK, the hair follicle matrix lineage fails to develop, likely due to abnormalities in development of apical–basal cell polarity, as well as in laminin-511 and basement membrane assembly at the tip of the hair bud. These defects also result in impaired specification of hair matrix and absence of precortex and inner sheath root cell lineages. The molecular pathways affected in ILK-deficient follicles are similar to those in the absence of epidermal integrin β1 and include Wnt, but not sonic hedgehog, signaling. ILK-deficient hair buds also show abnormalities in the dermal papilla. Addition of exogenous laminin-511 restores morphological and molecular markers associated with hair matrix formation, indicating that ILK regulates hair bud cell polarity and functions upstream from laminin-511 assembly to regulate the developmental progression of hair follicles beyond the germ stage. PMID:24371086

Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury.

PubMed

Nakrieko, Kerry-Ann; Rudkouskaya, Alena; Irvine, Timothy S; D'Souza, Sudhir J A; Dagnino, Lina

2011-07-15

Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15--expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury.

Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury

PubMed Central

Nakrieko, Kerry-Ann; Rudkouskaya, Alena; Irvine, Timothy S.; D'souza, Sudhir J. A.; Dagnino, Lina

2011-01-01

Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15–expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury. PMID:21593206

Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life.

PubMed

Miranda, Benjamin H; Charlesworth, Matthew R; Tobin, Desmond J; Sharpe, David T; Randall, Valerie A

2018-02-01

Male sex hormones-androgens-regulate male physique development. Without androgen signaling, genetic males appear female. During puberty, increasing androgens harness the hair follicle's unique regenerative ability to replace many tiny vellus hairs with larger, darker terminal hairs ( e.g., beard). Follicle response is epigenetically varied: some remain unaffected ( e.g., eyelashes) or are inhibited, causing balding. How sex steroid hormones alter such developmental processes is unclear, despite high incidences of hormone-driven cancer, hirsutism, and alopecia. Unfortunately, existing development models are not androgen sensitive. Here, we use hair follicles to establish an androgen-responsive human organ culture model. We show that women's intermediate facial follicles respond to men's higher androgen levels by synthesizing more hair over several days, unlike donor-matched, androgen-insensitive, terminal follicles. We demonstrate that androgen receptors-androgen-activated gene transcription regulators-are required and are present in vivo within these follicles. This is the first human organ that involves multiple cell types that responds appropriately to hormones in prolonged culture, in a way which mirrors its natural behavior. Thus, intermediate hair follicles offer a hormone-switchable human model with exceptional, unique availability of genetically identical, but epigenetically hormone-insensitive, terminal follicles. This should enable advances in understanding sex steroid hormone signaling, gene regulation, and developmental and regenerative systems and facilitate better therapies for hormone-dependent disorders.-Miranda, B. H., Charlesworth, M. R., Tobin, D. J., Sharpe, D. T., Randall, V. A. Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life.

Porokeratotic eccrine and hair follicle nevus: a report of two cases and review of the literature.

PubMed

Agulló-Pérez, Alfredo Daniel; Resano-Abarzuza, Miguel Ángel; Córdoba-Iturriagagoitia, Alicia; Yanguas-Bayona, Juan Ignacio

2017-01-01

Porokeratotic eccrine and hair follicle nevus is a very rare non-hereditary disorder of keratinization with eccrine and hair follicle involvement with only 9 cases described in the literature. In 2009 the term porokeratotic anexial ostial nevus was proposed to comprehend porokeratotic eccrine and hair follicle nevus and a related and more common process without follicular involvement: porokeratotic eccrine ostial and dermal duct nevus Recent findings suggest that both entities may be produced by a mutation in GJB2 gene, which is associated to KID syndrome. Herein we report 2 cases of porokeratotic eccrine and hair follicle nevus and review the existing cases in the Spanish and English literature.

A case of unilateral, systematized linear hair follicle nevi associated with epidermal nevus-like lesions.

PubMed

Ikeda, Shigaku; Kawada, Juri; Yaguchi, Hitoshi; Ogawa, Hideoki

2003-01-01

Multiple hair follicle nevi are an extremely rare condition. In 1998, a case of unilateral multiple hair follicle nevi, ipsilateral alopecia and ipsilateral leptomeningeal angiomatosis of the brain was first reported from Japan. Very recently, hair follicle nevus in a distribution following Blaschko's lines has also been reported. In this paper, we observed a congenital case of unilateral, systematized linear hair follicle nevi associated with congenital, ipsilateral, multiple plaque lesions resembling epidermal nevi but lacking leptomeningeal angiomatosis of the brain. These cases implicate the possibility of a novel neurocutaneous syndrome. Additional cases should be sought in order to determine whether this condition is pathophysiologically distinct. Copyright 2003 S. Karger AG, Basel

Hair follicle nevus in a 2-year old.

PubMed

Motegi, Sei-ichiro; Amano, Hiroo; Tamura, Atsushi; Ishikawa, Osamu

2008-01-01

We report a 2-year-old boy with an elastic soft, flatly elevated, skin-colored nodule on his nasal ala. Histologic examination revealed numerous small hair follicles in several stages of maturation in the dermis. Serial sections did not show any cartilage or a central epithelial lined cystic structure. Based on clinico-pathologic findings, we diagnosed this lesion as a hair follicle nevus. Hair follicle nevus is quite rare. Histologically, it is very important not to find cartilage or a central epithelial lined cystic structure for distinction from an accessory auricle and from a trichofolliculoma, respectively. Awareness of the clinical and pathologic characterization of hair follicle nevus is an aid to a correct diagnosis.

Porokeratotic eccrine and hair follicle nevus: a report of two cases and review of the literature*

PubMed Central

Agulló-Pérez, Alfredo Daniel; Resano-Abarzuza, Miguel Ángel; Córdoba-Iturriagagoitia, Alicia; Yanguas-Bayona, Juan Ignacio

2017-01-01

Porokeratotic eccrine and hair follicle nevus is a very rare non-hereditary disorder of keratinization with eccrine and hair follicle involvement with only 9 cases described in the literature. In 2009 the term porokeratotic anexial ostial nevus was proposed to comprehend porokeratotic eccrine and hair follicle nevus and a related and more common process without follicular involvement: porokeratotic eccrine ostial and dermal duct nevus Recent findings suggest that both entities may be produced by a mutation in GJB2 gene, which is associated to KID syndrome. Herein we report 2 cases of porokeratotic eccrine and hair follicle nevus and review the existing cases in the Spanish and English literature. PMID:29267468

Hybrid eccrine gland and hair follicle hamartoma: a new entity of adnexal nevus.

PubMed

Luo, Di-Qing; Huang, Chang-Zheng; Xie, Wen-Lin; Xu, Feng-Feng; Mo, Li-Qiu

2015-02-01

Eccrine nevus shows increase in number or size of eccrine glands, whereas hair follicle nevus is composed of densely packed normal vellus hairs, and eccrine-pilar angiomatous nevus reveals increase of eccrine, pilar, and angiomatous structures. No case with increased number of both eccrine glands and hair follicles only in the dermis has been previously reported. A 10-month-old girl presented with cutaneous hamartoma with overlying skin hyperpigmentation on her left hypochondrium since 3 months of age, in whom the lesion was completely excised. Histopathology demonstrated evidently increased number of both eccrine glands and hair follicles in the dermis with reactive hyperplasia of collagen fibers. No recurrence occurred after the tumor was completely excised. A term "hybrid eccrine gland and hair follicle hamartoma" is proposed for this unique lesion.

Long-Term Extensive Ectopic Hair Growth on the Spinal Cord of Mice from Transplanted Whisker Follicles.

PubMed

Cao, Wenluo; Li, Lingna; Mii, Sumiyuki; Amoh, Yasuyuki; Liu, Fang; Hoffman, Robert M

2015-01-01

We have previously demonstrated that hair follicles contain nestin-expressing pluripotent stem cells that can effect nerve and spinal cord repair upon transplantation. In the present study, isolated whisker follicles from nestin-driven green fluorescent protein (ND-GFP) mice were histocultured on Gelfoam for 3 weeks for the purpose of transplantation to the spinal cord to heal an induced injury. The hair shaft was cut off from Gelfoam-histocultured whisker follicles, and the remaining part of the whisker follicles containing GFP-nestin expressing pluripotent stem cells were transplanted into the injured spinal cord of nude mice, along with the Gelfoam. After 90 days, the mice were sacrificed and the spinal cord lesion was observed to have healed. ND-GFP expression was intense at the healed area of the spinal cord, as observed by fluorescence microscopy, demonstrating that the hair follicle stem cells were involved in healing the spinal cord. Unexpectedly, the transplanted whisker follicles sprouted out remarkably long hair shafts in the spinal cord during the 90 days after transplantation of Gelfoam whisker histocultures to the injured spine. The pigmented hair fibers, grown from the transplanted whisker histocultures, curved and enclosed the spinal cord. The unanticipated results demonstrate the great potential of hair growth after transplantation of Gelfoam hair follicle histocultures, even at an ectopic site.

Recent Advances in the Pathogenesis of Autoimmune Hair Loss Disease Alopecia Areata

PubMed Central

2013-01-01

Alopecia areata is considered to be a cell-mediated autoimmune disease, in which autoreactive cytotoxic T cells recognize melanocyte-associated proteins such as tyrosinase. This review discusses recent advances in the understanding of the pathogenesis of alopecia areata, focusing on immunobiology and hormonal aspects of hair follicles (HFs). The HF is a unique “miniorgan” with its own immune and hormonal microenvironment. The immunosuppressive milieu of the anagen hair bulb modulated by immunosuppressive factors is known as “hair follicle immune privilege.” The collapse of the hair follicle immune privilege leads to autoimmune reactions against hair follicle autoantigens. Alopecia areata is sometimes triggered by viral infections such as influenza that causes excess production of interferons (IFN). IFN-γ is one of the key factors that lead to the collapse of immune privilege. This paper reviews the interactions between the endocrine and immune systems and hair follicles in the pathogenesis of alopecia areata. PMID:24151515

Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration.

PubMed

Plikus, Maksim V; Mayer, Julie Ann; de la Cruz, Damon; Baker, Ruth E; Maini, Philip K; Maxson, Robert; Chuong, Cheng-Ming

2008-01-17

In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge are regulated by the surrounding microenvironment, or niche. The activation of such stem cells is cyclic, involving periodic beta-catenin activity. In the adult mouse, regeneration occurs in waves in a follicle population, implying coordination among adjacent follicles and the extrafollicular environment. Here we show that unexpected periodic expression of bone morphogenetic protein 2 (Bmp2) and Bmp4 in the dermis regulates this process. This BMP cycle is out of phase with the WNT/beta-catenin cycle, thus dividing the conventional telogen into new functional phases: one refractory and the other competent for hair regeneration, characterized by high and low BMP signalling, respectively. Overexpression of noggin, a BMP antagonist, in mouse skin resulted in a markedly shortened refractory phase and faster propagation of the regenerative wave. Transplantation of skin from this mutant onto a wild-type host showed that follicles in donor and host can affect their cycling behaviours mutually, with the outcome depending on the equilibrium of BMP activity in the dermis. Administration of BMP4 protein caused the competent region to become refractory. These results show that BMPs may be the long-sought 'chalone' inhibitors of hair growth postulated by classical experiments. Taken together, results presented in this study provide an example of hierarchical regulation of local organ stem cell homeostasis by the inter-organ macroenvironment. The expression of Bmp2 in subcutaneous adipocytes indicates physiological integration between these two thermo-regulatory organs. Our findings have practical importance for studies using mouse skin as a model for carcinogenesis, intra-cutaneous drug delivery and stem cell engineering studies, because they highlight the acute need to differentiate supportive versus inhibitory regions in the host skin.

Analysis of the expression pattern of the carrier protein transthyretin and its receptor megalin in the human scalp skin and hair follicles: hair cycle-associated changes.

PubMed

Adly, Mohamed A

2010-12-01

Transthyretin is a serum and cerebrospinal fluid protein synthesized early in development by the liver, choroid plexus and several other tissues. It is a carrier protein for the antioxidant vitamins, retinol, and thyroid hormones. Transthyretin helps internalize thyroxine and retinol-binding protein into cells by binding to megalin, which is a multi-ligand receptor expressed on the luminal surface of various epithelia. We investigated the expression of transthyretin and its receptor megalin in the human skin; however, their expression pattern in the hair follicle is still to be elucidated. This study addresses this issue and tests the hypothesis that "the expression of transthyretin and megalin undergoes hair follicle cycle-dependent changes." A total of 50 normal human scalp skin biopsies were examined (healthy females, 53-62 years) using immunofluorescence staining methods and real-time PCR. In each case, 50 hair follicles were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). Transthyretin and megalin were prominently expressed in the human scalp skin and hair follicles, on both gene and protein levels. The concentrations of transthyretin and megalin were 0.12 and 0.03 Ul/ml, respectively, as indicated by PCR. The expression showed hair follicle cycle-associated changes i.e., strong expression during early and mature anagen, very weak expression during catagen and moderate expression during telogen. The expression values of these proteins in the anagen were statistically significantly higher than those of either catagen or telogen hair follicles (P ≤ 0.001). This study provides the first morphologic indication that transthyretin and megalin are variably expressed in the human scalp skin and hair follicles. It also reports variations in the expression of these proteins during hair follicle cycling. The clinical ramifications of these findings are open for further investigations.

Activating Hair Follicle Stem Cells via R-spondin2 to Stimulate Hair Growth.

PubMed

Smith, Andrew A; Li, Jingtao; Liu, Bo; Hunter, Daniel; Pyles, Malcolm; Gillette, Martin; Dhamdhere, Girija R; Abo, Arie; Oro, Anthony; Helms, Jill A

2016-08-01

Wnt signaling is required for the development of the hair follicle, and for inciting the growth (anagen) phase of the hair cycle. Most strategies to enhance Wnt signaling for hair growth create a state of constitutive Wnt activation, which leads to neoplastic transformation of the epithelial hair matrix. Using Axin2(LacZ/+) and Axin2(Cre/+)R26R(mTmG/+) reporter mice and RNA analyses, we show that Wnt signaling is elevated during anagen, is reduced at the onset of catagen, and can be reamplified in the skin and surrounding hair follicles via intradermal injection of recombinant R-spondin2 protein. Using Lgr5(LacZ/+) reporter mice, we demonstrate that this amplified Wnt environment leads to activation of leucine-rich repeat-containing G-protein coupled receptor 5-positive stem cells in the hair follicle. The onset of catagen is repressed by R-spondin2 injection, and the anagen phase persists. As a consequence, hair shafts grow longer. We conclude that R-spondin2 treatment activates hair follicle stem cells and therefore may have therapeutic potential to promote hair growth. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

p53 Involvement in the Control of Murine Hair Follicle Regression

PubMed Central

Botchkarev, Vladimir A.; Komarova, Elena A.; Siebenhaar, Frank; Botchkareva, Natalia V.; Sharov, Andrei A.; Komarov, Pavel G.; Maurer, Marcus; Gudkov, Andrei V.; Gilchrest, Barbara A.

2001-01-01

p53 is a transcription factor mediating a variety of biological responses including apoptotic cell death. p53 was recently shown to control apoptosis in the hair follicle induced by ionizing radiation and chemotherapy, but its role in the apoptosis-driven physiological hair follicle regression (catagen) remains to be elucidated. Here, we show that p53 protein is strongly expressed and co-localized with apoptotic markers in the regressing hair follicle compartments during catagen. In contrast to wild-type mice, p53 knockout mice show significant retardation of catagen accompanied by significant decrease in the number of apoptotic cells in the hair matrix. Furthermore, p53 null hair follicles are characterized by alterations in the expression of markers that are encoded by p53 target genes and are implicated in the control of catagen (Bax, Bcl-2, insulin-like growth factor binding protein-3). These data suggest that p53 is involved in the control of apoptosis in the hair follicle during physiological regression and imply that p53 antagonists may be useful for the management of hair growth disorders characterized by premature entry into catagen, such as androgenetic alopecia, alopecia areata, and telogen effluvium. PMID:11395365

Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Yujing; Nakanishi, Masako; Sato, Fuyuki

Highlights: • The number of secondary hair follicles is reduced by half in Trps1 KO embryonic skin compared to wild-type skin. • Noggin expression is significantly decreased and BMP signaling is promoted in Trps1 KO embryonic skin. • Treatment with a Noggin or BMP inhibitor rescued the decreased number of hair follicles in Trps1 KO skin graft cultures. • Cell proliferation and apoptosis of the epidermis were normalized by Noggin treatment. - Abstract: A representative phenotype of patients with tricho-rhino-phalangeal syndrome (TRPS) is sparse hair. To understand the developmental defects of these patient’s hair follicles, we analyzed the development ofmore » hair follicles histologically and biochemically using Trps1 deficient (KO) mice. First, we compared the numbers of primary hair follicles in wild-type (WT) and KO embryos at different developmental stages. No differences were observed in the E14.5 skins of WT and KO mice. However, at later time points, KO fetal skin failed to properly develop secondary hair follicles, and the number of secondary hair follicles present in E18.5 KO skin was approximately half compared to that of WT skin. Sonic hedgehog expression was significantly decreased in E17.5 KO skin, whereas no changes were observed in Eda/Edar expression in E14.5 or E17.5 skins. In addition, Noggin expression was significantly decreased in E14.5 and E17.5 KO skin compared to WT skin. In parallel with the suppression of Noggin expression, BMP signaling was promoted in the epidermal cells of KO skins compared to WT skins as determined by immunohistochemistry for phosphorylated Smad1/5/8. The reduced number of secondary hair follicles was restored in skin graft cultures treated with a Noggin and BMP inhibitor. Furthermore, decreased cell proliferation, and increased apoptosis in KO skin was rescued by Noggin treatment. Taken together, we conclude that hair follicle development in Trps1 KO embryos is impaired directly or indirectly by decreased Noggin expression.« less

Hair follicle nevus occurring in frontonasal dysplasia: an electron microscopic observation.

PubMed

Kuwahara, H; Lao, L M; Kiyohara, T; Kumakiri, M; Igawa, H

2001-06-01

We report a rare hair follicle nevus that occurred in a three-month-old Japanese boy with mild frontonasal dysplasia. It had been present since birth. Histologically, numerous tiny vellus hair follicles were found within the dermis. The constituent cells of these follicles showed the features of follicular germ cells under the electron microscope. The fibroblasts around the follicles were active and merged with the colloid substance. Many myofibroblasts were found in a collagenous stroma in the atrophic lesion of the frontonasal dysplasia.

Expression of fox-related genes in the skin follicles of Inner Mongolia cashmere goat.

PubMed

Han, Wenjing; Li, Xiaoyan; Wang, Lele; Wang, Honghao; Yang, Kun; Wang, Zhixin; Wang, Ruijun; Su, Rui; Liu, Zhihong; Zhao, Yanhong; Zhang, Yanjun; Li, Jinquan

2018-03-01

This study investigated the expression of genes in cashmere goats at different periods of their fetal development. Bioinformatics analysis was used to evaluate data obtained by transcriptome sequencing of fetus skin samples collected from Inner Mongolia cashmere goats on days 45, 55, and 65 of fetal age. We found that FoxN1 , FoxE1 , and FoxI3 genes of the Fox gene family were probably involved in the growth and development of the follicle and the formation of hair, which is consistent with previous findings. Real-time quantitative polymerase chain reaction detecting system and Western blot analysis were employed to study the relative differentially expressed genes FoxN1 , FoxE1 , and FoxI3 in the body skin of cashmere goat fetuses and adult individuals. This study provided new fundamental information for further investigation of the genes related to follicle development and exploration of their roles in hair follicle initiation, growth, and development.

Isolation of Mouse Hair Follicle Bulge Stem Cells and Their Functional Analysis in a Reconstitution Assay.

PubMed

Zheng, Ying; Hsieh, Jen-Chih; Escandon, Julia; Cotsarelis, George

2016-01-01

The hair follicle (HF) is a dynamic structure readily accessible within the skin, and contains various pools of stem cells that have a broad regenerative potential during normal homeostasis and in response to injury. Recent discoveries demonstrating the multipotent capabilities of hair follicle stem cells and the easy access to skin tissue make the HF an attractive source for isolating stem cells and their subsequent application in tissue engineering and regenerative medicine. Here, we describe the isolation and purification of hair follicle bulge stem cells from mouse skin, and hair reconstitution assays that allows the functional analysis of multipotent stem cells.

Development of a Model for Chemotherapy-Induced Alopecia: Profiling of Histological Changes in Human Hair Follicles after Chemotherapy.

PubMed

Yoon, Ji-Seon; Choi, Mira; Shin, Chang Yup; Paik, Seung Hwan; Kim, Kyu Han; Kwon, Ohsang

2016-03-01

Optimized research models are required to further understand the pathogenesis and prophylaxis of chemotherapy-induced alopecia. Our aim was to develop a mouse model for chemotherapy-induced alopecia by follicular unit transplantation of human hair follicles onto immunodeficient mice. Twenty-two weeks after transplantation, a single dose of cyclophosphamide (Cph) was administered to mice in the Cph100 (100 mg/kg) and Cph150 (150 mg/kg) groups. On day 6, hair follicles showed dystrophic changes, with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, upregulated expression of apoptotic regulators [P53, Fas/Fas-ligand, tumor necrosis factor-related apoptosis-inducing ligand/tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL/TRAIL receptor), and Bax], increased apoptotic matrix keratinocytes, downregulated Ki67 expression, and decreased melanogenic protein in the hair bulb were noted in both groups. After 12 treatment days, hair follicles in Cph100 mice appeared to diminish dystrophic changes. In contrast, hair follicles of Cph150 mice prematurely entered a dystrophic catagen phase after 9 treatment days, and immunofluorescence staining for Ki67 and melanogenic protein expressions was barely visible. Two hair follicle damage response pathways were observed in this model, namely dystrophic anagen (Cph100) and catagen (Cph150) pathways. Our model might be useful for further understanding the impact of chemotherapy on human hair follicles. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Morphological analysis of patchy thickening and reddish discoloration of active hair growth areas in the skin of New Zealand White rabbits.

PubMed

Ishihara, Tomoko; Yamashita, Haruhiro; Sakurai, Takanobu; Morita, Junya; Sakamoto, Kouji; Ishii, Aiko; Sasaki, Minoru

2017-10-01

Patchy thickening and reddish discoloration of active hair growth areas of skin in rabbits are occasionally found, and this gross feature could affect precise evaluation when conducting a dermal irritation test. Since little is known about the mechanism of this phenomenon, we examined the dorsal skin of New Zealand White rabbits morphologically and immunohistochemically in order to identify the possible mechanism responsible for developing these skin changes in relation to the hair cycle. Skin samples from 4 rabbits were divided into three groups (5 samples/group) based on their macroscopic characteristics: a thickened skin, erythematous skin, and smooth skin group. Histomorphological examination revealed that the percentage of hair follicles in the anagen phase, hair follicle length, hair follicle area, and proliferating cell nuclear antigen-positive cells in the hair follicles were greater in the thickened skin and erythematous skin groups than in the smooth skin group. Unlike mice and rats, the dermis was nearly adjacent to the muscular layer with a thin hypodermis, and the whole lengths of hair follicles in the anagen phase were located in the dermis in the rabbit skin. These results suggest that large hair follicles in the anagen phase compressed the surrounding dermis; therefore, the skin was grossly raised and showed thickening. A higher number of CD31-positive blood vessels, suggesting the occurrence of angiogenesis, was observed around the hair follicles in the erythematous skin group, and they seemed to affect the reddish discoloration of skin noted grossly.

Hair Follicular Expression and Function of Group X Secreted Phospholipase A2 in Mouse Skin*

PubMed Central

Yamamoto, Kei; Taketomi, Yoshitaka; Isogai, Yuki; Miki, Yoshimi; Sato, Hiroyasu; Masuda, Seiko; Nishito, Yasumasa; Morioka, Kiyokazu; Ishimoto, Yoshikazu; Suzuki, Noriko; Yokota, Yasunori; Hanasaki, Kohji; Ishikawa, Yukio; Ishii, Toshiharu; Kobayashi, Tetsuyuki; Fukami, Kiyoko; Ikeda, Kazutaka; Nakanishi, Hiroki; Taguchi, Ryo; Murakami, Makoto

2011-01-01

Although perturbed lipid metabolism can often lead to skin abnormality, the role of phospholipase A2 (PLA2) in skin homeostasis is poorly understood. In the present study we found that group X-secreted PLA2 (sPLA2-X) was expressed in the outermost epithelium of hair follicles in synchrony with the anagen phase of hair cycling. Transgenic mice overexpressing sPLA2-X (PLA2G10-Tg) displayed alopecia, which was accompanied by hair follicle distortion with reduced expression of genes related to hair development, during a postnatal hair cycle. Additionally, the epidermis and sebaceous glands of PLA2G10-Tg skin were hyperplasic. Proteolytic activation of sPLA2-X in PLA2G10-Tg skin was accompanied by preferential hydrolysis of phosphatidylethanolamine species with polyunsaturated fatty acids as well as elevated production of some if not all eicosanoids. Importantly, the skin of Pla2g10-deficient mice had abnormal hair follicles with noticeable reduction in a subset of hair genes, a hypoplasic outer root sheath, a reduced number of melanin granules, and unexpected up-regulation of prostanoid synthesis. Collectively, our study highlights the spatiotemporal expression of sPLA2-X in hair follicles, the presence of skin-specific machinery leading to sPLA2-X activation, a functional link of sPLA2-X with hair follicle homeostasis, and compartmentalization of the prostanoid pathway in hair follicles and epidermis. PMID:21266583

Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouji, Yukiteru; Yoshikawa, Masahide; Shiroi, Akira

2006-06-30

We previously showed that Wnt-10b promoted the differentiation of primary skin epithelial cells (MPSEC) toward hair shaft and inner root sheath of the hair follicle (IRS) cells in vitro. In the present study, we found that Wnt-10b promotes the development of hair follicles using a culture of mouse embryonic skin tissue and trichogenesis using a reconstitution experiment with nude mice. Hair follicle development was observed in skin taken from mouse embryos on embryonic day 10.5 following a 2-day culture with recombinant Wnt-10b (rWnt-10b), however, not without rWnt-10b. Brown hair growth was observed at the site of reconstituted skin in Balb/cmore » nude mice where dermal fibroblasts and keratinocytes, derived from C3H/HeN new born mice, were transplanted with Wnt-10b-producing COS cells (Wnt-COS). Without the co-transplantation of Wnt-COS, no hair growth was observed. Our results suggest an important role of Wnt-10b in the initiation of hair follicle development and following trichogenesis.« less

Expression of Mineralized Tissue Associated Proteins: Dentin Sialoprotein and Phosphophoryn in Rodent Hair Follicles

PubMed Central

Tang, Xu-na; Zhu, Ya-qin; Marcelo, Cynthia L.; Ritchie, Helena H.

2012-01-01

Background Mammalian hair development and tooth development are controlled by a series of reciprocal epithelial-mesenchymal interactions. Similar growth factors and transcription factors, such as fibroblast growth factor (FGF), sonic hedgehog homolog (SHH), bone morphogenetic proteins (BMPs) and Wnt10a, were reported to be involved in both of these interactions. Dentin sialoprotein (DSP) and phosphophoryn (PP) are the two major non-collagenous proteins secreted by odontoblasts that participate in dentin mineralization during tooth development. Because of striking similarities between tooth development and hair follicle development, we investigated whether DSP and/or PP proteins may also play a role in hair follicle development. Objective In this study, we examined the presence and location of DSP/PP proteins during hair follicle development. Methods Rat PP proteins were detected using immunohistochemical/immunofluorescent staining. DSP-PP mRNAs were detected by in situ hybridization with riboprobes. LacZ expression was detected in mouse tissues using a DSP-PP promoter-driven LUC in transgenic mice. Results We found that PP proteins and DSP-PP mRNAs are present in rat hair follicles. We also demonstrate that an 8 kb DSP-PP promoter is able to drive lacZ expression in hair follicles. Conclusion We have firmly established the presence of DSP/PP in mouse and rat hair follicles by immunohistochemical/immunofluorescent staining, in situ hybridization with riboprobes and transgenic mice studies. The expression of DSP/PP in hair follicles is the first demonstration that major mineralization proteins likely may also contribute to soft tissue development. This finding opens a new avenue for future investigations into the molecular-genetic management of soft tissue development. PMID:21908176

Expression of mineralized tissue associated proteins: dentin sialoprotein and phosphophoryn in rodent hair follicles.

PubMed

Tang, Xu-na; Zhu, Ya-qin; Marcelo, Cynthia L; Ritchie, Helena H

2011-11-01

Mammalian hair development and tooth development are controlled by a series of reciprocal epithelial-mesenchymal interactions. Similar growth factors and transcription factors, such as fibroblast growth factor (FGF), sonic hedgehog homolog (SHH), bone morphogenetic proteins (BMPs) and Wnt10a, were reported to be involved in both of these interactions. Dentin sialoprotein (DSP) and phosphophoryn (PP) are the two major non-collagenous proteins secreted by odontoblasts that participate in dentin mineralization during tooth development. Because of striking similarities between tooth development and hair follicle development, we investigated whether DSP and/or PP proteins may also play a role in hair follicle development. In this study, we examined the presence and location of DSP/PP proteins during hair follicle development. Rat PP proteins were detected using immunohistochemical/immunofluorescent staining. DSP-PP mRNAs were detected by in situ hybridization with riboprobes. LacZ expression was detected in mouse tissues using a DSP-PP promoter-driven LUC in transgenic mice. We found that PP proteins and DSP-PP mRNAs are present in rat hair follicles. We also demonstrate that an 8 kb DSP-PP promoter is able to drive lacZ expression in hair follicles. We have firmly established the presence of DSP/PP in mouse and rat hair follicles by immunohistochemical/immunofluorescent staining, in situ hybridization with riboprobes and transgenic mice studies. The expression of DSP/PP in hair follicles is the first demonstration that major mineralization proteins likely may also contribute to soft tissue development. This finding opens a new avenue for future investigations into the molecular-genetic management of soft tissue development. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Skin transcriptome reveals the intrinsic molecular mechanisms underlying hair follicle cycling in Cashmere goats under natural and shortened photoperiod conditions.

PubMed

Yang, Min; Song, Shen; Dong, Kunzhe; Chen, XiaoFei; Liu, Xuexue; Rouzi, Marhaba; Zhao, Qianjun; He, Xiaohong; Pu, Yabin; Guan, Weijun; Ma, Yuehui; Jiang, Lin

2017-10-18

The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. However, the underlying molecular mechanism remains unclear. We profiled the skin transcriptome of six goats at seven time points during hair follicle cycling via RNA-seq. The six goats comprised three goats exposed to a natural photoperiod and three exposed to a shortened photoperiod. During hair cycle transition, 1713 genes showed differential expression, and 332 genes showed a pattern of periodic expression. Moreover, a short photoperiod induced the hair follicle to enter anagen early, and 246 genes overlapped with the periodic genes. Among these key genes, cold-shock domain containing C2 (CSDC2) was highly expressed in the epidermis and dermis of Cashmere goat skin, although its function in hair-follicle development remains unknown. CSDC2 silencing in mouse fibroblasts resulted in the decreased mRNA expression of two key hair-follicle factors, leading to reduced cell numbers and a lower cell density. Cashmere growth or molting might be controlled by a set of periodic regulatory genes. The appropriate management of short light exposure can induce hair follicles to enter full anagen early through the activation of these regulators. The CSDC2 gene is a potentially important transcription factor in the hair growth cycle.

Dietary vitamin A regulates wingless-related MMTV integration site signaling to alter the hair cycle.

PubMed

Suo, Liye; Sundberg, John P; Everts, Helen B

2015-05-01

Alopecia areata (AA) is an autoimmune hair loss disease caused by a cell-mediated immune attack of the lower portion of the cycling hair follicle. Feeding mice 3-7 times the recommended level of dietary vitamin A accelerated the progression of AA in the graft-induced C3H/HeJ mouse model of AA. In this study, we also found that dietary vitamin A, in a dose dependent manner, activated the hair follicle stem cells (SCs) to induce the development and growth phase of the hair cycle (anagen), which may have made the hair follicle more susceptible to autoimmune attack. Our purpose here is to determine the mechanism by which dietary vitamin A regulates the hair cycle. We found that vitamin A in a dose-dependent manner increased nuclear localized beta-catenin (CTNNB1; a marker of canonical wingless-type Mouse Mammary Tumor Virus integration site family (WNT) signaling) and levels of WNT7A within the hair follicle bulge in these C3H/HeJ mice. These findings suggest that feeding mice high levels of dietary vitamin A increases WNT signaling to activate hair follicle SCs. © 2014 by the Society for Experimental Biology and Medicine.

Bulge Region as a Putative Hair Follicle Stem Cells Niche: A Brief Review

PubMed Central

JOULAI VEIJOUYE, Sanaz; YARI, Abazar; HEIDARI, Fatemeh; SAJEDI, Nayereh; GHOROGHI MOGHANI, Fatemeh; NOBAKHT, Maliheh

2017-01-01

Background: Hair follicle stem cells exist in different sites. Most of the hair follicle stem cells are reside in niche called bulge. Bulge region is located between the opening of sebaceous gland and the attachment site of the arrector pili muscle. Methods: Data were collected using databases and resources of PubMed, Web of Science, Science Direct, Scopus, MEDLINE and their references from the earliest available published to identify English observational studies on hair follicle bulge region. Results: Bulge stem cells are pluripotent with high proliferative capacity. Specific markers allow the bulge cells to be isolated from mouse or human hair follicle. Stem cells isolated from bulge region are label retaining and slow cycling hence these cells are defined as label-retaining cells. Bulge cell populations, due to their plasticity nature are able to differentiate into distinct linage and could contribute in tissue regeneration. Conclusion: The current review discuss about bulge stem cells characteristics and biology including their cycle, location, plasticity, specific markers and regenerative nature. Also the differences between mouse and human hair follicles are investigated. PMID:29026781

Unscheduled DNA synthesis in human hair follicles after in vitro exposure to 11 chemicals: comparison with unscheduled DNA synthesis in rat hepatocytes.

PubMed

van Erp, Y H; Koopmans, M J; Heirbaut, P R; van der Hoeven, J C; Weterings, P J

1992-06-01

A new method is described to investigate unscheduled DNA synthesis (UDS) in human tissue after exposure in vitro: the human hair follicle. A histological technique was applied to assess cytotoxicity and UDS in the same hair follicle cells. UDS induction was examined for 11 chemicals and the results were compared with literature findings for UDS in rat hepatocytes. Most chemicals inducing UDS in rat hepatocytes raised DNA repair at comparable concentrations in the hair follicle. However, 1 of 9 chemicals that gave a positive response in the rat hepatocyte UDS test, 2-acetylaminofluorene, failed to induce DNA repair in the hair follicle. Metabolizing potential of hair follicle cells was shown in experiments with indirectly acting compounds, i.e., benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene and dimethylnitrosamine. The results support the conclusion that the test in its present state is valuable as a screening assay for the detection of unscheduled DNA synthesis. Moreover, the use of human tissues may result in a better extrapolation to man.

l-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase.

PubMed

Kwack, M H; Shin, S H; Kim, S R; Im, S U; Han, I S; Kim, M K; Kim, J C; Sung, Y K

2009-06-01

l-Ascorbic acid 2-phosphate (Asc 2-P), a derivative of l-ascorbic acid, promotes elongation of hair shafts in cultured human hair follicles and induces hair growth in mice. To investigate whether the promotion of hair growth by Asc 2-P is mediated by insulin-like growth factor-1 (IGF-1) and, if so, to investigate the mechanism of the Asc 2-P-induced IGF-1 expression. Dermal papilla (DP) cells were cultured and IGF-1 level was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay after Asc 2-P treatment in the absence or presence of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Also, hair shaft elongation in cultured human scalp hair follicles and proliferation of cocultured keratinocytes were examined after Asc 2-P treatment in the absence or presence of neutralizing antibody against IGF-1. In addition, keratinocyte proliferation in cultured hair follicles after Asc 2-P treatment in the absence or presence of LY294002 was examined by Ki-67 immunostaining. IGF-1 mRNA in DP cells was upregulated and IGF-1 protein in the conditioned medium of DP cells was significantly increased after treatment with Asc 2-P. Immunohistochemical staining showed that IGF-1 staining is increased in the DP of cultured human hair follicles by Asc 2-P. The neutralizing antibody against IGF-1 significantly suppressed the Asc 2-P-mediated elongation of hair shafts in hair follicle organ culture and significantly attenuated Asc 2-P-induced growth of cocultured keratinocytes. LY294002 significantly attenuated Asc 2-P-inducible IGF-1 expression and proliferation of follicular keratinocytes in cultured hair follicles. These data show that Asc 2-P-inducible IGF-1 from DP cells promotes proliferation of follicular keratinocytes and stimulates hair follicle growth in vitro via PI3K.

Mouse models for human hair loss disorders

PubMed Central

Porter, Rebecca M

2003-01-01

The outer surface of the hand, limb and body is covered by the epidermis, which is elaborated into a number of specialized appendages, evolved not only to protect and reinforce the skin but also for social signalling. The most prominent of these appendages is the hair follicle. Hair follicles are remarkable because of their prolific growth characteristics and their complexity of differentiation. After initial embryonic morphogenesis, the hair follicle undergoes repeated cycles of regression and regeneration throughout the lifetime of the organism. Studies of mouse mutants with hair loss phenotypes have suggested that the mechanisms controlling the hair cycle probably involve many of the major signalling molecules used elsewhere in development, although the complete pathway of hair follicle growth control is not yet understood. Mouse studies have also led to the discovery of genes underlying several human disorders. Future studies of mouse hair-loss mutants are likely to benefit the understanding of human hair loss as well as increasing our knowledge of mechanisms controlling morphogenesis and tumorigenesis. PMID:12587927

Genetics Home Reference: alopecia areata

MedlinePlus

... areata the immune system targets hair follicles , stopping hair growth. However, the condition does not permanently damage the follicles, which is why hair may later regrow. Many of the genes that ...

Contribution of the Hair Follicular Pathway to Total Skin Permeation of Topically Applied and Exposed Chemicals

PubMed Central

Mohd, Fadli; Todo, Hiroaki; Yoshimoto, Masato; Yusuf, Eddy; Sugibayashi, Kenji

2016-01-01

Generally, the blood and skin concentration profiles and steady-state skin concentration of topically applied or exposed chemicals can be calculated from the in vitro skin permeation profile. However, these calculation methods are particularly applicable to chemicals for which the main pathway is via the stratum corneum. If the contribution of hair follicles to the total skin permeation of chemicals can be obtained in detail, their blood and skin concentrations can be more precisely predicted. In the present study, the contribution of the hair follicle pathway to the skin permeation of topically applied or exposed chemicals was calculated from the difference between their permeability coefficients through skin with and without hair follicle plugging, using an in vitro skin permeation experiment. The obtained results reveal that the contribution of the hair follicle pathway can be predicted by using the chemicals’ lipophilicity. For hydrophilic chemicals (logarithm of n-octanol/water partition coefficient (log Ko/w) < 0), a greater reduction of permeation due to hair follicle plugging was observed than for lipophilic chemicals (log Ko/w ≥ 0). In addition, the ratio of this reduction was decreased with an increase in log Ko/w. This consideration of the hair follicle pathway would be helpful to investigate the efficacy and safety of chemicals after topical application or exposure to them because skin permeation and disposition should vary among skins in different body sites due to differences in the density of hair follicles. PMID:27854289

Contribution of the Hair Follicular Pathway to Total Skin Permeation of Topically Applied and Exposed Chemicals.

PubMed

Mohd, Fadli; Todo, Hiroaki; Yoshimoto, Masato; Yusuf, Eddy; Sugibayashi, Kenji

2016-11-15

Generally, the blood and skin concentration profiles and steady-state skin concentration of topically applied or exposed chemicals can be calculated from the in vitro skin permeation profile. However, these calculation methods are particularly applicable to chemicals for which the main pathway is via the stratum corneum. If the contribution of hair follicles to the total skin permeation of chemicals can be obtained in detail, their blood and skin concentrations can be more precisely predicted. In the present study, the contribution of the hair follicle pathway to the skin permeation of topically applied or exposed chemicals was calculated from the difference between their permeability coefficients through skin with and without hair follicle plugging, using an in vitro skin permeation experiment. The obtained results reveal that the contribution of the hair follicle pathway can be predicted by using the chemicals' lipophilicity. For hydrophilic chemicals (logarithm of n -octanol/water partition coefficient (log K o/w ) < 0), a greater reduction of permeation due to hair follicle plugging was observed than for lipophilic chemicals (log K o/w ≥ 0). In addition, the ratio of this reduction was decreased with an increase in log K o/w . This consideration of the hair follicle pathway would be helpful to investigate the efficacy and safety of chemicals after topical application or exposure to them because skin permeation and disposition should vary among skins in different body sites due to differences in the density of hair follicles.

Hair Follicle Nevus Located on the Chin of an Infant: Case Report and Review of Literature.

PubMed

Larson, Krista N; O'Shea, Patrick; Zedek, Daniel C; Morrell, Dean S

2016-01-01

Hair follicle nevi are rare, benign, congenital hamartomas that usually occur in the distribution of the first brachial arch. Histopathologically, the distinction between hair follicle nevus, trichofolliculoma, and accessory tragus has recently come into question, and it may be that they are all on a spectrum of the same condition. We report the case of a 7-day-old boy who presented with a "tag"-like lesion on his midline chin that had been present since birth. Biopsy of the lesion proved it to be a hair follicle nevus. © 2016 Wiley Periodicals, Inc.

Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: an update.

PubMed

Nakamura, Motonobu; Schneider, Marlon R; Schmidt-Ullrich, Ruth; Paus, Ralf

2013-01-01

Human hair disorders comprise a number of different types of alopecia, atrichia, hypotrichosis, distinct hair shaft disorders as well as hirsutism and hypertrichosis. Their causes vary from genodermatoses (e.g. hypotrichoses) via immunological disorders (e.g. alopecia areata, autoimmune cicatrical alopecias) to hormone-dependent abnormalities (e.g. androgenetic alopecia). A large number of spontaneous mouse mutants and genetically engineered mice develop abnormalities in hair follicle morphogenesis, cycling, and/or hair shaft formation, whose analysis has proven invaluable to define the molecular regulation of hair growth, ranging from hair follicle development, and cycling to hair shaft formation and stem cell biology. Also, the accumulating reports on hair phenotypes of mouse strains provide important pointers to better understand the molecular mechanisms underlying human hair growth disorders. Since numerous new mouse mutants with a hair phenotype have been reported since the publication of our earlier review on this matter a decade ago, we present here an updated, tabulated mini-review. The updated annotated tables list a wide selection of mouse mutants with hair growth abnormalities, classified into four categories: Mutations that affect hair follicle (1) morphogenesis, (2) cycling, (3) structure, and (4) mutations that induce extrafollicular events (for example immune system defects) resulting in secondary hair growth abnormalities. This synthesis is intended to provide a useful source of reference when studying the molecular controls of hair follicle growth and differentiation, and whenever the hair phenotypes of a newly generated mouse mutant need to be compared with existing ones. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Follicular dermal papilla structures by organization of epithelial and mesenchymal cells in interfacial polyelectrolyte complex fibers.

PubMed

Lim, Tze Chiun; Leong, Meng Fatt; Lu, Hongfang; Du, Chan; Gao, Shujun; Wan, Andrew C A; Ying, Jackie Y

2013-09-01

The hair follicle is a regenerating organ that produces a new hair shaft during each growth cycle. Development and cycling of the hair follicle is governed by interactions between the epithelial and mesenchymal components. Therefore, development of an engineered 3D hair follicle would be useful for studying these interactions to identify strategies for treatment of hair loss. We have developed a technique suitable for assembly of different cell types in close proximity in fibrous hydrogel scaffolds with resolutions of ∼50 μm. By assembly of dermal papilla (DP) and keratinocytes, structures similar to the native hair bulb arrangement are formed. Gene expression of these constructs showed up-regulation of molecules involved in epithelial-mesenchymal interactions of the hair follicle. Implantation of the follicular structures in SCID mice led to the formation of hair follicle-like structures, thus demonstrating their hair inductive ability. The transparency of the fiber matrix and the small dimensions of the follicular structures allowed the direct quantitation of DP cell proliferation by confocal microscopy, clearly illustrating the promoting or inhibitory effects of hair growth regulating agents. Collectively, our results suggested a promising application of these 3D engineered follicular structures for in vitro screening and testing of drugs for hair growth therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

CD34 Expression by Hair Follicle Stem Cells Is Required for Skin Tumor Development in Mice

PubMed Central

Trempus, Carol S.; Morris, Rebecca J.; Ehinger, Matthew; Elmore, Amy; Bortner, Carl D.; Ito, Mayumi; Cotsarelis, George; Nijhof, Joanne G.W.; Peckham, John; Flagler, Norris; Kissling, Grace; Humble, Margaret M.; King, Leon C.; Adams, Linda D.; Desai, Dhimant; Amin, Shantu; Tennant, Raymond W.

2007-01-01

The cell surface marker CD34 marks mouse hair follicle bulge cells, which have attributes of stem cells, including quiescence and multipotency. Using a CD34 knockout (KO) mouse, we tested the hypothesis that CD34 may participate in tumor development in mice because hair follicle stem cells are thought to be a major target of carcinogens in the two-stage model of mouse skin carcinogenesis. Following initiation with 200 nmol 7,12-dimethylbenz(a)anthracene (DMBA), mice were promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Under these conditions, CD34KO mice failed to develop papillomas. Increasing the initiating dose of DMBA to 400 nmol resulted in tumor development in the CD34KO mice, albeit with an increased latency and lower tumor yield compared with the wild-type (WT) strain. DNA adduct analysis of keratinocytes from DMBA-initiated CD34KO mice revealed that DMBA was metabolically activated into carcinogenic diol epoxides at both 200 and 400 nmol. Chronic exposure to TPA revealed that CD34KO skin developed and sustained epidermal hyperplasia. However, CD34KO hair follicles typically remained in telogen rather than transitioning into anagen growth, confirmed by retention of bromodeoxyuridine-labeled bulge stem cells within the hair follicle. Unique localization of the hair follicle progenitor cell marker MTS24 was found in interfollicular basal cells in TPA-treated WT mice, whereas staining remained restricted to the hair follicles of CD34KO mice, suggesting that progenitor cells migrate into epidermis differently between strains. These data show that CD34 is required for TPA-induced hair follicle stem cell activation and tumor formation in mice. PMID:17483328

Gene expression profiling in psoriatic scalp hair follicles: clobetasol propionate shampoo 0.05% normalizes psoriasis disease markers.

PubMed

Aubert, J; Reiniche, P; Fogel, P; Poulin, Y; Lui, H; Lynde, C; Shapiro, J; Villemagne, H; Soto, P; Voegel, J J

2010-11-01

Clobetasol propionate shampoo is effective and safe in treatment of scalp psoriasis (SP). Gene expression profiling of psoriatic skin biopsies led to the identification of numerous disease-related genes. However, it remained unknown whether the gene expression profile of hair follicles of SP patients was also affected. To determine whether psoriasis-related genes are differentially regulated in the hair follicles of SP patients and whether the modulation of these genes can be correlated with clinical severity scores. A single arm, open study was conducted in three centres. SP patients received daily treatment with clobetasol propionate shampoo. At Baseline, Weeks 2 and 4, investigators assessed clinical severity parameters and collected scalp hair follicles in anagen phase. Total RNA extracted from hair follicles was used to determine the expression level of 44 genes, which were reported previously to be upregulated in the skin of psoriasis patients. RNA of good quality and sufficient quantity was obtained from hair follicles of psoriasis patients and healthy volunteers (HV). The expression level of 10 inflammation-related genes was significantly increased in psoriatic hair follicles. The patient's exploratory transcriptomic score, defined as the mean fold modulation of these 10 genes compared with HV, correlated with clinical severity scores. Clobetasol propionate shampoo was effective in decreasing both the exploratory transcriptomics and the clinical severity scores. Hair follicles of SP patients are affected by the inflammatory process. The change in the expression level of inflammation-related genes correlates with the severity of the disease. © 2010 Galderma R&D. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Reflections on how wound healing-promoting effects of the hair follicle can be translated into clinical practice.

PubMed

Jimenez, Francisco; Poblet, Enrique; Izeta, Ander

2015-02-01

Clinicians have long reported that hair-bearing areas tend to heal more rapidly than those lacking hair follicles. In the past decade, numerous scientific studies have corroborated clinical evidence, showing a direct nexus between the human hair follicle and the wound healing process. The migration of epithelial follicular stem cells to the skin surface to help in the wound re-epithelialization and the effect of the hair cycle on the wound healing rate underline the influence of the hair follicle in the healing process. In clinical practice, non-healing wounds are pathologies of high prevalence with significant associated burden costs for the healthcare system. As the population ages, the prevalence of this pathology is expected to increase in future years. The recent advances in understanding the biology of hair follicle stem cells have created the challenges of using this newly acquired knowledge in practical therapeutic applications. Chronic leg ulcers are an example of the targeted pathologies that urgently need better therapies. In this essay, our aim is to raise interest in this question, reviewing what is known in relation to the connections between hair follicles and wound healing, and elaborating on future directions that the field might take, including implications for clinical practice. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

7-Phloroeckol promotes hair growth on human follicles in vitro.

PubMed

Bak, Soon-Sun; Sung, Young Kwan; Kim, Se-Kwon

2014-08-01

7-Phloroeckol, phloroglucinol derivative isolated from marine brown algae, has anti-oxidative, anti-inflammatory responses and MMP inhibitory activities. In this study, we evaluated the hair growth-promoting effects of 7-phloroeckol in human hair follicles. To investigate cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells in the presence or absence of 7-phloroeckol treatment, MTT assay was employed. Moreover, gene expression and protein concentration of insulin-like growth factor (IGF)-1 was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. 7-Phloroeckol induced an increase in proliferation of DPCs and ORS cells. In addition, hair shaft growth was measured using the hair-follicle organ culture system. 7-Phloroeckol resulted in elongation of the hair shaft in cultured human hair follicles. 7-Phloroeckol induced an IGF-1 mRNA expression and protein concentration in DPCs and conditioned media, respectively. These results suggest that 7-phloroeckol promotes hair growth through stimulation of DPCs and ORS cells.

Porokeratotic eccrine duct and hair follicle nevus (PEHFN) associated with keratitis-ichthyosis-deafness (KID) syndrome.

PubMed

Criscione, Vincent; Lachiewicz, Anne; Robinson-Bostom, Leslie; Grenier, Nicole; Dill, Sara Worthing

2010-01-01

Porokeratotic eccrine ostial and dermal duct nevus is a rare hamartomatous malformation, histologically characterized by cornoid lamellae overlying dilated eccrine ostia. The nevus most commonly presents in the form of multiple filiform keratotic spines in a linear arrangement, usually on the distal extremities. Porokeratotic eccrine and hair follicle nevus is thought to be a variant of porokeratotic eccrine ostial and dermal duct nevus that additionally involves hair follicle infundibula. We report a case of widespread Porokeratotic eccrine and hair follicle nevus that developed in a 15-year-old woman with keratitis-ichthyosis-deafness syndrome. © 2010 Wiley Periodicals, Inc.

Ratchet effect for nanoparticle transport in hair follicles.

PubMed

Radtke, Matthias; Patzelt, Alexa; Knorr, Fanny; Lademann, Jürgen; Netz, Roland R

2017-07-01

The motion of a single rigid nanoparticle inside a hair follicle is investigated by means of Brownian dynamics simulations. The cuticular hair structure is modeled as a periodic asymmetric ratchet-shaped surface. Induced by oscillating radial hair motion we find directed nanoparticle transport into the hair follicle with maximal velocity at a specific optimal frequency and an optimal particle size. We observe flow reversal when switching from radial to axial oscillatory hair motion. We also study the diffusion behavior and find strongly enhanced diffusion for axial motion with a diffusivity significantly larger than for free diffusion. Copyright © 2016 Elsevier B.V. All rights reserved.

Topical application of nanoparticles: prospects and safety aspects (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lademann, Jürgen M.; Richter, Heike; Jung, Sora; Meinke, Martina C.; Rühl, Eckart; Alexiev, Ulrike; Calderon, Marcelo; Patzelt, Alexa

2016-03-01

The requirements on nanoparticles for cosmetic and medical applications are very different. While nanoparticles applied in sunscreens shall remain on the skin surface or in the upper cell layers of the stratum corneum, nanoparticles for medical drug delivery shall penetrate through the skin barrier to the target structures in the living cells. Under the Collaborative Research Project 1112 various methods are used at the CCP to investigate the cutaneous penetration and storage of nanoparticles, hair follicles being in the focus of attention. Human hair follicles are ideal target structures for drug delivery. Hosting both the stem and dendritic cells, they are surrounded by a dense network of blood vessels. Investigating nanoparticles of different size and materials, particles of approximately 600 nm in diameter were found to penetrate best into the hair follicles, where they can be stored for maximally 10 days. Their retention time in the hair follicles exceeds that in the stratum corneum by almost one order of magnitude. Particles penetrate more efficiently into the hair follicles than non-particulate substances. For particles from 40 nm-1 µm in diameter, however, no follicular penetration has been detectable if the skin barrier was intact. This is plausible as the hair follicle has its own barrier. It will be demonstrated that the best way for drug delivery is the application of drug-loaded particulate carrier systems. In the hair follicles the particles may either dissolve and release the drug, or an external signal must trigger the drug release from the particle.

Human hair pigmentation--biological aspects.

PubMed

Tobin, D J

2008-08-01

Skin and hair colour contribute significantly to our overall visual appearance and to social/sexual communication. Despite their shared origins in the embryologic neural crest, the hair follicle and epidermal pigmentary units occupy distinct, although open, cutaneous compartments. They can be distinguished principally on the basis of the former's stringent coupling to the hair growth cycle compared with the latter's continuous melanogenesis. The biosynthesis of melanin and its subsequent transfer from melanocyte to hair bulb keratinocytes depend on the availability of melanin precursors and on a raft of signal transduction pathways that are both highly complex and commonly redundant. These signalling pathways can be both dependent and independent of receptors, act through auto-, para- or intracrine mechanisms and can be modified by hormonal signals. Despite many shared features, follicular melanocytes appear to be more sensitive than epidermal melanocytes to ageing influences. This can be seen most dramatically in hair greying/canities and this is likely to reflect significant differences in the epidermal and follicular microenvironments. The hair follicle pigmentary unit may also serve as an important environmental sensor, whereby hair pigment contributes to the rapid excretion of heavy metals, chemicals and toxins from the body by their selective binding to melanin; rendering the hair fibre a useful barometer of exposures. The recent availability of advanced cell culture methodologies for isolated hair follicle melanocytes and for intact anagen hair follicle organ culture should provide the research tools necessary to elucidate the regulatory mechanisms of hair follicle pigmentation. In the longer term, it may be feasible to develop hair colour modifiers of a biological nature to accompany those based on chemicals.

Unravelling hair follicle-adipocyte communication.

PubMed

Schmidt, Barbara; Horsley, Valerie

2012-11-01

Here, we explore the established and potential roles for intradermal adipose tissue in communication with hair follicle biology. The hair follicle delves deep into the rich dermal macroenvironment as it grows to maturity where it is surrounded by large lipid-filled adipocytes. Intradermal adipocytes regenerate with faster kinetics than other adipose tissue depots and in parallel with the hair cycle, suggesting an interplay exists between hair follicle cells and adipocytes. While adipocytes have well-established roles in metabolism and energy storage, until recently, they were overlooked as niche cells that provide important growth signals to neighbouring skin cells. We discuss recent data supporting adipocytes as niche cells for the skin and skin pathologies that may be related to alterations in skin adipose tissue defects. © 2012 John Wiley & Sons A/S.

Hair growth-promoting activity of hot water extract of Thuja orientalis.

PubMed

Zhang, Nan-nan; Park, Dong Ki; Park, Hye-Jin

2013-01-10

Thuja orientalis has been traditionally used to treat patients who suffer from baldness and hair loss in East Asia. The present study sought to investigate the hair growth-promoting activity of T. orientalis hot water extract and the underlying mechanism of action. After T. orientalis extract was topically applied to the shaved dorsal skin of telogenic C57BL/6 N mice, the histomorphometric analysis was employed to study induction of the hair follicle cycle. To determine the effect of T. orientalis extract on the telogen to anagen transition, the protein expression levels of β-catenin and Sonic hedgehog (Shh) in hair follicles were determined by immunohistochemistry. We observed that T. orientalis extract promoted hair growth by inducing the anagen phase in telogenic C57BL/6 N mice. Specifically, the histomorphometric analysis data indicates that topical application of T. orientalis extract induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to either the control or 1% minoxidil-treated group. We also observed increases in both the number and size of hair follicles of the T. orientalis extract-treated group. Moreover, the immunohistochemical analysis reveals earlier induction of β-catenin and Shh proteins in hair follicles of the T. orientalis extract-treated group, compared to the control or 1% minoxidil-treated group. These results suggest that T. orientalis extract promotes hair growth by inducing the anagen phase in resting hair follicles and might therefore be a potential hair growth-promoting agent.

Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration

PubMed Central

Zhen, Hanson H.; Oro, Anthony E.

2013-01-01

Hair follicle morphogenesis, a complex process requiring interaction between epithelia-derived keratinocytes and the underlying mesenchyme, is an attractive model system to study organ development and tissue-specific signaling. Although hair follicle development is genetically tractable, fast and reproducible analysis of factors essential for this process remains a challenge. Here we describe a procedure to generate targeted overexpression or shRNA-mediated knockdown of factors using lentivirus in a tissue-specific manner. Using a modified version of a hair regeneration model 5, 6, 11, we can achieve robust gain- or loss-of-function analysis in primary mouse keratinocytes or dermal cells to facilitate study of epithelial-mesenchymal signaling pathways that lead to hair follicle morphogenesis. We describe how to isolate fresh primary mouse keratinocytes and dermal cells, which contain dermal papilla cells and their precursors, deliver lentivirus containing either shRNA or cDNA to one of the cell populations, and combine the cells to generate fully formed hair follicles on the backs of nude mice. This approach allows analysis of tissue-specific factors required to generate hair follicles within three weeks and provides a fast and convenient companion to existing genetic models. PMID:23486463

Structure and expression of genes for a class of cysteine-rich proteins of the cuticle layers of differentiating wool and hair follicles

PubMed Central

1990-01-01

The major histological components of the hair follicle are the hair cortex and cuticle. The hair cuticle cells encase and protect the cortex and undergo a different developmental program to that of the cortex. We report the molecular characterization of a set of evolutionarily conserved hair genes which are transcribed in the hair cuticle late in follicle development. Two genes were isolated and characterized, one expressed in the human follicle and one in the sheep follicle. Each gene encodes a small protein of 16 kD, containing greater than 50 cysteine residues, ranging from 31 to 36 mol% cysteine. Their high cysteine content and in vitro expression data identify them as ultra-high-sulfur (UHS) keratin proteins. The predicted proteins are composed almost entirely of cysteine-rich and glycine-rich repeats. Genomic blots reveal that the UHS keratin proteins are encoded by related multigene families in both the human and sheep genomes. Tissue in situ hybridization demonstrates that the expression of both genes is localized to the hair fiber cuticle and occurs at a late stage in fiber morphogenesis. PMID:1703541

Compartmentation of Mitochondrial and Oxidative Metabolism in Growing Hair Follicles: A Ring of Fire.

PubMed

Lemasters, John J; Ramshesh, Venkat K; Lovelace, Gregory L; Lim, John; Wright, Graham D; Harland, Duane; Dawson, Thomas L

2017-07-01

Little is known about the energetics of growing hair follicles, particularly in the mitochondrially abundant bulb. Here, mitochondrial and oxidative metabolism was visualized by multiphoton and light sheet microscopy in cultured bovine hair follicles and plucked human hairs. Mitochondrial membrane potential (ΔΨ), cell viability, reactive oxygen species (ROS), and secretory granules were assessed with parameter-indicating fluorophores. In growing follicles, lower bulb epithelial cells had high viability, and mitochondria were polarized. Most epithelially generated ROS co-localized with polarized mitochondria. As the imaging plane captured more central and distal cells, ΔΨ disappeared abruptly at a transition to a nonfluorescent core continuous with the hair shaft. Approaching the transition, ΔΨ and ROS increased, and secretory granules disappeared. ROS and ΔΨ were strongest in a circumferential paraxial ring at putative sites for formation of the outer cortex/cuticle of the hair shaft. By contrast, polarized mitochondria in dermal papillar fibroblasts produced minimal ROS. Plucked hairs showed a similar abrupt transition of degranulation/depolarization near sites of keratin deposition, as well as an ROS-generating paraxial ring of fire. Hair movement out of the follicle appeared to occur independently of follicular bulb bioenergetics by a tractor mechanism involving the inner and outer root sheaths. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Roles of GasderminA3 in Catagen-Telogen Transition During Hair Cycling.

PubMed

Bai, Xiufeng; Lei, Mingxing; Shi, Jiazhong; Yu, Yu; Qiu, Weiming; Lai, Xiangdong; Liu, Yingxin; Yang, Tian; Yang, Li; Widelitz, Randall B; Chuong, Cheng-Ming; Lian, Xiaohua

2015-09-01

Hair follicles undergo cyclic behavior through regression (catagen), rest (telogen), and regeneration (anagen) during postnatal life. The hair cycle transition is strictly regulated by the autonomous and extrinsic molecular environment. However, whether there is a switch controlling catagen-telogen transition remains largely unknown. Here we show that hair follicles cycle from catagen to the next anagen without transitioning through a morphologically typical telogen after Gsdma3 mutation. This leaves an ESLS (epithelial strand-like structure) during the time period corresponding to telogen phase in WT mice. Molecularly, Wnt10b is upregulated in Gsdma3 mutant mice. Restoration of Gsdma3 expression in AE (alopecia and excoriation) mouse skin rescues hair follicle telogen entry and significantly decreases the Wnt10b-mediated Wnt/β-catenin signaling pathway. Overexpression of Wnt10b inhibits telogen entry by increasing epithelial strand cell proliferation. Subsequently, hair follicles with a Gsdma3 mutation enter the second anagen simultaneously as WT mice. Hair follicles cannot enter the second anagen with ectopic WT Gsdma3 overexpression. A luciferase reporter assay proves that Gsdma3 directly suppresses Wnt signaling. Our findings suggest that Gsdma3 has an important role in catagen-telogen transition by balancing the Wnt signaling pathway and that morphologically typical telogen is not essential for the initiation of a new hair cycle.

Roles of GasderminA3 in catagen- telogen transition during hair cycling

PubMed Central

Bai, Xiufeng; Lei, Mingxing; Shi, Jiazhong; Yu, Yu; Qiu, Weiming; Lai, Xiangdong; Liu, Yingxin; Yang, Tian; Yang, Li; Widelitz, Randall Bruce; Chuong, Cheng-Ming; Lian, Xiaohua

2015-01-01

Hair follicles undergo cyclic behavior through regression (catagen), rest (telogen) and regeneration (anagen) during postnatal life. The hair cycle transition is strictly regulated by the autonomous and extrinsic molecular environment. However, whether there is a switch controlling catagen-telogen transition remains largely unknown. Here we show that hair follicles cycle from catagen to the next anagen without transitioning through a morphologically typical telogen after Gsdma3 mutation. This leaves an ESLS (epithelial strand-like structure) during the time period corresponding to telogen phase in WT mice. Molecularly, Wnt10b is upregulated in Gsdma3 mutant mice. Restoration of Gsdma3 expression in AE (alopecia and excoriation) mouse skin rescues hair follicle telogen entry and significantly decreases the Wnt10b-mediated Wnt/β-catenin signaling pathway. Overexpression of Wnt10b inhibits telogen entry by increasing epithelial strand cell proliferation. Subsequently, hair follicles with a Gsdma3 mutation enter the second anagen simultaneously as WT mice. Hair follicles cannot enter the second anagen with ectopic WT Gsdma3 overexpression. A luciferase reporter assay proves Gsdma3 directly suppresses Wnt signaling. Our findings suggest Gsdma3 plays an important role in catagen-telogen transition by balancing the Wnt signaling pathway, and that morphologically typical telogen is not essential for the initiation of a new hair cycle. PMID:25860385

Isolation and Quantification of Glycosaminoglycans from Human Hair Shaft

PubMed Central

Bonovas, Stefanos; Sitaras, Nikolaos

2016-01-01

Background There is evidence that glycosaminoglycans (GAGs) are present in the hair shaft within the follicle but there are no studies regarding GAGs isolation and measurement in the human hair shaft over the scalp surface, it means, in the free hair shaft. Objective The purpose of our research was to isolate and measure the total GAGs from human free hair shaft. Methods Seventy-five healthy individuals participated in the study, 58 adults, men and women over the age of 50 and 17 children (aged 4~9). GAGs in hair samples, received from the parietal and the occipital areas, were isolated with 4 M guanidine HCl and measured by the uronic acid-carbazole reaction assay. Results GAGs concentration was significantly higher in the occipital area than in the parietal area, in all study groups. GAG levels from both areas were significantly higher in children than in adults. GAG levels were not associated with gender, hair color or type. Conclusion We report the presence of GAGs in the human free hair shaft and the correlation of hair GAG levels with the scalp area and participants' age. PMID:27746630

[Hair growth effect of minoxidil].

PubMed

Otomo, Susumu

2002-03-01

The length and size of hair are depend on the anagen term in its hair cycle. It has been reported that the some cell growth factors, such as VEGF, FGF-5S, IGF-1 and KGF, induce the proliferation of cells in the matrix, dermal papilla and dermal papillary vascular system and increase the amount of extra cellular matrix in dermal papilla and then maintain follicles in the anagen phase. On the other hand, negative factors, like FGF-5, thrombospondin, or still unknown ones, terminate the anagen phase. If the negative factors become dominant against cell proliferation factors according to fulfilling some time set by the biological clock for hair follicles, TGF beta induced in the matrix tissues evokes apoptosis of matrix cells and shifts the follicles from anagen to catagen. Androgenetic alopecia is caused by miniaturizing of hair follicles located in the frontal or crown part of scalp and are hereditarily more sensitive to androgen. In their hair cycles, the androgen shortens the anagen phase of follicles and shifts them to the catagen phase earlier than usual. The mode of action of hair growth effect of minoxidil is not completely elucidated, but the most plausible explanation proposed here is that minoxidil works as a sulfonylurea receptor (SUR) activator and prolongs the anagen phase of hair follicles in the following manner: minoxidil (1) induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells, (2) inhibits of TGF beta induced apoptosis of hair matrix cells by opening the Kir 6.0 channel pore coupled with SUR on the mitochondrial inner membrane, and (3) dilates hair follicle arteries and increases blood flow in dermal papilla by opening the Kir 6.0 channel pore coupled with SUR on the plasma membrane of vascular smooth muscle cells.

The longest telomeres: a general signature of adult stem cell compartments

PubMed Central

Flores, Ignacio; Canela, Andres; Vera, Elsa; Tejera, Agueda; Cotsarelis, George; Blasco, María A.

2008-01-01

Identification of adult stem cells and their location (niches) is of great relevance for regenerative medicine. However, stem cell niches are still poorly defined in most adult tissues. Here, we show that the longest telomeres are a general feature of adult stem cell compartments. Using confocal telomere quantitative fluorescence in situ hybridization (telomapping), we find gradients of telomere length within tissues, with the longest telomeres mapping to the known stem cell compartments. In mouse hair follicles, we show that cells with the longest telomeres map to the known stem cell compartments, colocalize with stem cell markers, and behave as stem cells upon treatment with mitogenic stimuli. Using K15-EGFP reporter mice, which mark hair follicle stem cells, we show that GFP-positive cells have the longest telomeres. The stem cell compartments in small intestine, testis, cornea, and brain of the mouse are also enriched in cells with the longest telomeres. This constitutes the description of a novel general property of adult stem cell compartments. Finally, we make the novel finding that telomeres shorten with age in different mouse stem cell compartments, which parallels a decline in stem cell functionality, suggesting that telomere loss may contribute to stem cell dysfunction with age. PMID:18283121

Female Pattern Hair Loss: a clinical and pathophysiological review*

PubMed Central

Ramos, Paulo Müller; Miot, Hélio Amante

2015-01-01

Female Pattern Hair Loss or female androgenetic alopecia is the main cause of hair loss in adult women and has a major impact on patients' quality of life. It evolves from the progressive miniaturization of follicles that lead to a subsequent decrease of the hair density, leading to a non-scarring diffuse alopecia, with characteristic clinical, dermoscopic and histological patterns. In spite of the high frequency of the disease and the relevance of its psychological impact, its pathogenesis is not yet fully understood, being influenced by genetic, hormonal and environmental factors. In addition, response to treatment is variable. In this article, authors discuss the main clinical, epidemiological and pathophysiological aspects of female pattern hair loss. PMID:26375223

Coexistence of esophageal blue nevus, hair follicles and basaloid sqamous carcinoma: a case report.

PubMed

Wang, Dong-Guan; Li, Xin-Gong; Gao, Hong; Sun, Xi-Yin; Zhou, Xiao-Qiu

2008-07-14

We present the case of a 57-year-old man who underwent esophagectomy for esophageal carcinoma found at barium meal and gastroscopic examination. He was diagnosed as esophageal basaloid squamous carcinoma (BSC) and gastric stromal tumor, which were associated with focal proliferation of melanocytes/pigmentophages and hair follicles in esophageal mucosa. Melanocytic hyperplasia (melanocytosis) has previously been recognized as an occasional reactive lesion, which can accompany esophageal inflammation and invasive squamous carcinoma. The present case is unusual because of its hyperplasia of not only melanocytes but also hair follicles. To our knowledge, this is the first report of esophageal blue nevus and hair follicle coexisting with BSC.

Genetics Home Reference: androgenetic alopecia

MedlinePlus

... in both males and females, such as regulating hair growth and sex drive. Hair growth begins under the skin in structures called follicles. ... follicles can lead to a shorter cycle of hair growth and the growth of shorter and thinner strands ...

Aging of the Hair Follicle Pigmentation System

PubMed Central

Tobin, Desmond J

2009-01-01

Skin and hair phenotypes are powerful cues in human communication. They impart much information, not least about our racial, ethnic, health, gender and age status. In the case of the latter parameter, we experience significant change in pigmentation in our journey from birth to puberty and through to young adulthood, middle age and beyond. The hair follicle pigmentary unit is perhaps one of our most visible, accessible and potent aging sensors, with marked dilution of pigment intensity occurring long before even subtle changes are seen in the epidermis. This dichotomy is of interest as both skin compartments contain melanocyte subpopulations of similar embryologic (i.e., neural crest) origin. Research groups are actively pursuing the study of the differential aging of melanocytes in the hair bulb versus the epidermis and in particular are examining whether this is in part linked to the stringent coupling of follicular melanocytes to the hair growth cycle. Whether some follicular melanocyte subpopulations are affected, like epidermal melanocytes, by UV irradiation is not yet clear. A particular target of research into hair graying or canities is the nature of the melanocyte stem compartment and whether this is depleted due to reactive oxygen species-associated damage, coupled with an impaired antioxidant status, and a failure of melanocyte stem cell renewal. Over the last few years, we and others have developed advanced in vitro models and assay systems for isolated hair follicle melanocytes and for intact anagen hair follicle organ culture which may provide research tools to elucidate the regulatory mechanisms of hair follicle pigmentation. Long term, it may be feasible to develop strategies to modulate some of these aging-associated changes in the hair follicle that impinge particularly on the melanocyte populations. PMID:20927229

Enhanced Expansion and Sustained Inductive Function of Skin‐Derived Precursor Cells in Computer‐Controlled Stirred Suspension Bioreactors

PubMed Central

Agabalyan, Natacha A.; Borys, Breanna S.; Sparks, Holly D.; Boon, Kathryn; Raharjo, Eko W.; Abbasi, Sepideh; Kallos, Michael S.

2016-01-01

Abstract Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isolated and grown in vitro as self‐renewing colonies called skin‐derived precursors (SKPs). Following transplantation into skin, SKPs can generate new dermis and reconstitute the dermal papilla and connective tissue sheath, suggesting they could have important therapeutic value for the treatment of skin disease (alopecia) or injury. Controlled cell culture processes must be developed to efficiently and safely generate sufficient stem cell numbers for clinical use. Compared with static culture, stirred‐suspension bioreactors generated fivefold greater expansion of viable SKPs. SKPs from each condition were able to repopulate the dermal stem cell niche within established hair follicles. Both conditions were also capable of inducing de novo hair follicle formation and exhibited bipotency, reconstituting the dermal papilla and connective tissue sheath, although the efficiency was significantly reduced in bioreactor‐expanded SKPs compared with static conditions. We conclude that automated bioreactor processing could be used to efficiently generate large numbers of autologous DSCs while maintaining their inherent regenerative function. Stem Cells Translational Medicine 2017;6:434–443 PMID:28191777

Inhibitory activities of some traditional Chinese herbs against testosterone 5α-reductase and effects of Cacumen platycladi on hair re-growth in testosterone-treated mice.

PubMed

Zhang, Bei; Zhang, Rong-weng; Yin, Xi-quan; Lao, Zi-zhao; Zhang, Zhe; Wu, Qing-guang; Yu, Liang-wen; Lai, Xiao-ping; Wan, Yu-hua; Li, Geng

2016-01-11

Many traditional Chinese medicines (TCM) have been used for hundreds of years for hair blackening and hair nourishing, and now many of them are commonly used in Chinese herbal shampoo to nourish the hair and promote hair growth. The present study was performed to screen 5α-reductase (5αR) inhibitors from traditional Chinese medicines, evaluate its hair growth promoting activity in vivo, and further investigate its effects on androgen metabolism and the expression of 5αR II in hair follicles. Nine TCM which were dried, ground and extracted by maceration with 75% ethanol or distilled water were used for screening 5αR inhibitors, and enzymes were extracted from the rat epididymis. The leaves of Platycladus orientalis (L.) Franco was used to evaluate the in vivo anti-androgenic activity. Skin color was observed daily and the hair re-growth was assessed by assigning the hair growth score. The longitudinal sections of hair follicles were used for observing follicle morphology, classifying of distinct stages of hair follicle morphogenesis and calculate the average score. The transverse sections were used for determination of hair follicle counts. Testosterone (T), Dihydrotestosterone (DHT) and Estradiol (E2) levels in serum and skin tissue were detected by ELISA kits. The immunofluorescence assay was used to detect the influence of CP-ext on 5αR expression in dorsal skin. We found the extract of Ganoderma lucidum (GL-ext), Polygonum multiflori (PM-ext), Cacumen platycladi (CP-ext) and Cynomorium songaricum (CS-ext) showed stronger 5αR inhibitory activity. CP-ext (5mg and 2mg/mouse/day) could significantly shorten the time of the dorsal skin darkening and got longhaired (P<0.01), and showed high hair re-growth promoting activity. Furthermore the histological data of hair follicles in each group showed that CP-ext could promote the growth of hair follicle and slowed down hair follicles enter the telogen. What's more CP-ext significantly reduced DHT levels and down-regulated the expression of 5αRⅡin skin (P<0.01). GL-ext, PM-ext, CP-ext and CS-ext showed strong 5αR inhibitory activity. CP-ext possesses high hair growth promoting activity in the in vivo androgen-sensitive mouse model via inhibiting the 5αR activity, decreasing the DHT levels and in turn suppressing the expression of 5αR. Our study may contribute to the development of a new generation of herbal supplements with clearer material basis of pharmacodynamic for treating androgenic alopecia (AGA). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The in vitro use of the hair follicle closure technique to study the follicular and percutaneous permeation of topically applied drugs.

PubMed

Stahl, Jessica; Niedorf, Frank; Wohlert, Mareike; Kietzmann, Manfred

2012-03-01

Recent studies on follicular permeation emphasise the importance of hair follicles as diffusion pathways, but only a limited amount of data are available about the follicular permeation of topically applied drugs. This study examines the use of a hair follicle closure technique in vitro, to determine the participation of hair follicles in transdermal drug penetration. Various substances, with different lipophilicities, were tested: caffeine, diclofenac, flufenamic acid, ibuprofen, paracetamol, salicylic acid and testosterone. Diffusion experiments were conducted with porcine skin, the most common replacement material for human skin, in Franz-type diffusion cells over 28 hours. Different experimental settings allowed the differentiation between interfollicular and follicular permeation after topical application of the test compounds. A comparison of the apparent permeability coefficients of the drugs demonstrates that the percutaneous permeations of caffeine and flufenamic acid were significantly higher along the hair follicles. In the cases of paracetamol and testosterone, the follicular pathway appears to be of importance, while no difference was found between interfollicular and follicular permeation for diclofenac, ibuprofen and salicylic acid. Thus, the hair follicle closure technique represents an adequate in vitro method for gaining information about follicular or percutaneous permeation, and can replace in vivo testing in animals or humans. 2012 FRAME.

Ginsenoside Rg3 up-regulates the expression of vascular endothelial growth factor in human dermal papilla cells and mouse hair follicles.

PubMed

Shin, Dae Hyun; Cha, Youn Jeong; Yang, Kyeong Eun; Jang, Ik-Soon; Son, Chang-Gue; Kim, Bo Hyeon; Kim, Jung Min

2014-07-01

Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real-time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3-stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose-dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up-regulated by Rg3 in a dose-dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up-regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products. Copyright © 2013 John Wiley & Sons, Ltd.

Establishment of human hair follicle mesenchymal stem cells with overexpressed human hepatocyte growth factor.

PubMed

Zhou, Dan; Cheng, Hongjing; Liu, Jinyu; Zhang, Lei

2017-06-01

Chronic liver disease has become a major health problem that causes serious damage to human health. Since the existing treatment effect was not ideal, we need to seek new treatment methods. We utilized the gene recombination technology to obtain the human hair mesenchymal stem cells which overexpression of human hepatocyte growth factor (hHGF). Furthermore, we verified the property of transfected cells through detecting surface marker by flow cytometry. We show here establishment of the hHGF-overexpressing lentivirus vector, and successfully transfection to human hair follicle mesenchymal stem cells. The verified experiments could demonstrate the human hair follicle mesenchymal stem cells which have been transfected still have the properties of stem cells. We successfully constructed human hair follicle mesenchymal stem cells which overexpression hHGF, and maintain the same properties compared with pro-transfected cells.

Transfollicular delivery takes root: the future for vaccine design?

PubMed

Hansen, Steffi; Lehr, Claus-Michael

2014-01-01

The immunological environment of hair follicles has lately received the attention of researchers in the context of transfollicular drug delivery, particularly for improving needle-free transcutaneous immunization. Hair follicles represent shunt pathways across the stratum corneum barrier, which may facilitate the absorption of large or hydrophilic molecules such as vaccine antigens. Currently researchers have identified opportunities and challenges created by transfollicular vaccination. Nanotechnology may facilitate transfollicular delivery in several ways as nanoparticles penetrate deeper and to a higher extent into hair follicles than solutions. Also, nanoencapsulation can stabilize antigens and increase their antigenicity. This seems necessary as only a limited portion of topically applied antigen is available via the hair follicles and as the responsiveness of perifollicular Langerhans cells varies during hair cycle. These problems may be overcome by developing more efficient adjuvant-coupled nanocarriers with high antigen payload.

Hair follicle response of the golden Syrian hamster flank organ to continuous testosterone stimulation using silastic capsules.

PubMed

Lucky, A W; McGuire, J; Nydorf, E; Halpert, G; Nuck, B A

1986-01-01

The hamster flank organ has served as a model to study androgen-dependent responses of the skin, but the quantitative response of hair follicles to androgenic stimulation has been neglected. We assayed the hair follicle response to testosterone (T) and compared it to the response of the sebaceous glands and of the dermal pigment in the Golden Syrian hamster flank organ. Because of biologic variation in male animals and uneven absorption of hormone from parenteral injections, we implanted silastic capsules 0.25, 0.5, 1, and 2 cm in length filled with crystalline T subcutaneously into female hamsters for 6 weeks. Hair follicle response to T was more sensitive than sebaceous gland or pigment. Diameters of hairs under the sebaceous gland increased significantly from control values of 27.7 +/- 1.0 micron to 38.0 +/- 1.6 micron at the lowest dose of T tested, the 0.25-cm capsule (p less than 0.001). There was an increase in the absolute number of hairs under the sebaceous gland as the flank organ enlarged, from 27.9 +/- 9.9 control to 55.3 +/- 5.8 with the 2-cm T capsule. There was no concomitant increase in hair density, 14.4 +/- 3.5 hairs/mm control vs 12.5 +/- 1.1 hairs/mm with the 2-cm capsule. Hair follicles lateral to the sebaceous gland did not show the same response to androgen stimulation. Sebaceous gland and pigmentation responded in a dose-dependent fashion, the maximum effect being achieved with a 1-cm T capsule. We conclude that T affects hair by specifically stimulating growth of individual hairs physically under the sebaceous gland. As the whole flank organ enlarges more hairs are recruited to become larger but no new follicles appear. These studies also confirm that there are different sensitivities to androgen within the various androgen-dependent components of the hamster flank organ, with increase in hair diameter being highly sensitive. This model should be useful for the specific and quantitative assessment of androgenic and antiandrogenic substances on hair growth and ultimately by useful for therapy of hirsutism.

Full-thickness skin with mature hair follicles generated from tissue culture expanded human cells.

PubMed

Wu, Xunwei; Scott, Larry; Washenik, Ken; Stenn, Kurt

2014-12-01

The goal of regenerative medicine is to reconstruct fully functional organs from tissue culture expanded human cells. In this study, we report a method for human reconstructed skin (hRSK) when starting with human cells. We implanted tissue culture expanded human epidermal and dermal cells into an excision wound on the back of immunodeficient mice. Pigmented skin covered the wound 4 weeks after implantation. Hair shafts were visible at 12 weeks and prominent at 14 weeks. Histologically, the hRSK comprises an intact epidermis and dermis with mature hair follicles, sebaceous glands and most notably, and unique to this system, subcutis. Morphogenesis, differentiation, and maturation of the hRSK mirror the human fetal process. Human antigen markers demonstrate that the constituent cells are of human origin for at least 6 months. The degree of new skin formation is most complete when using tissue culture expanded cells from fetal skin, but it also occurs with expanded newborn and adult cells; however, no appendages formed when we grafted both adult dermal and epidermal cells. The hRSK system promises to be valuable as a laboratory model for studying biological, pathological, and pharmaceutical problems of human skin.

Parathyroid hormone-related peptide and the hair cycle - is it the agonists or the antagonists that cause hair growth?

PubMed

Gensure, Robert C

2014-12-01

While the effects of PTHrP have been studied for almost 20 years, most of these studies have focused on effects on the termination of the anagen phase, giving an incomplete picture of the overall effect of PTHrP on the hair cycle. PTHrP was determined in several experimental models to promote transition of hair follicles from anagen to catagen phase, which by itself would suggest that PTHrP blockade might prolong the anagen phase and promote hair growth. However, clinical trials with topically applied PTHrP antagonists have been disappointing, leading to a reconsideration of this model. Additional studies performed in mouse models where hair follicles are damaged (alopecia areata, chemotherapy-induced alopecia) suggest that PTHrP has effects early in the hair cycle as well, promoting hair follicles' entry into anagen phase and initiates the hair cycle. While the mechanism of this has yet to be elucidated, it may involve activation of the Wnt pathway. Thus, the overall effect of PTHrP is to stimulate and accelerate the hair cycle, and in the more clinically relevant models of hair loss where hair follicles have been damaged or become quiescent, it is the agonists, not the antagonists, which would be expected to promote hair growth. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alopecia areata

PubMed Central

Pratt, C. Herbert; King, Lloyd E.; Messenger, Andrew G.; Christiano, Angela M.; Sundberg, John P.

2017-01-01

Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair bearing sites. Patchy alopecia affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of alopecia areata affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models showed that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified associated with signaling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future. PMID:28300084

Icariin promotes mouse hair follicle growth by increasing insulin-like growth factor 1 expression in dermal papillary cells.

PubMed

Su, Y-S; Fan, Z-X; Xiao, S-E; Lin, B-J; Miao, Y; Hu, Z-Q; Liu, H

2017-04-01

Icariin is a major flavonoid isolated from Epimedium spp. leaves (Epimedium Herba), and has multiple pharmacological functions, including anti-angiogenesis, anti-oxidant, anti-inflammatory and immunoprotective effects. To investigate whether icariin can stimulate growth of hair follicles in mice and the underlying mechanism. In vitro, the effect of icariin on hair growth was assessed by using a vibrissae hair follicle (VHF) organ-culture model. The proliferation of hair matrix keratinocytes and the expression of insulin-like growth factor (IGF)-1 in follicles were examined by double immunostaining for 5-bromo-2'-deoxyuridine and IGF-1, in the presence or absence of icariin. Dermal papilla cells (DPCs) were cultured and IGF-1 level was measured by reverse transcription-PCR and ELISA after icariin treatment. In vivo, the effect of icariin on hair growth was examined by gavage feeding of icariin to mice whose backs had been depilated, and the conversion of telogen to anagen hair was observed. Treatment with icariin promoted hair shaft elongation, prolonged the hair cycle growth phase (anagen) in cultured VHFs, and accelerated transition of hair cycle from telogen to anagen phase in the dorsal skin of mice. There was significant proliferation of matrix keratinocytes and an increased level of IGF-1 in cultured VHFs. Moreover, icariin treatment upregulated IGF-1 mRNA expression in DPCs and increased IGF-1 protein content in the conditioned medium of DPCs. These results suggest that icariin can promote mouse hair follicle growth via stimulation of IGF-1 expression in DPCs. © 2017 British Association of Dermatologists.

Hair growth-promoting activity of hot water extract of Thuja orientalis

PubMed Central

2013-01-01

Background Thuja orientalis has been traditionally used to treat patients who suffer from baldness and hair loss in East Asia. The present study sought to investigate the hair growth-promoting activity of T. orientalis hot water extract and the underlying mechanism of action. Methods After T. orientalis extract was topically applied to the shaved dorsal skin of telogenic C57BL/6 N mice, the histomorphometric analysis was employed to study induction of the hair follicle cycle. To determine the effect of T. orientalis extract on the telogen to anagen transition, the protein expression levels of β-catenin and Sonic hedgehog (Shh) in hair follicles were determined by immunohistochemistry. Results We observed that T. orientalis extract promoted hair growth by inducing the anagen phase in telogenic C57BL/6 N mice. Specifically, the histomorphometric analysis data indicates that topical application of T. orientalis extract induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to either the control or 1% minoxidil-treated group. We also observed increases in both the number and size of hair follicles of the T. orientalis extract-treated group. Moreover, the immunohistochemical analysis reveals earlier induction of β-catenin and Shh proteins in hair follicles of the T. orientalis extract-treated group, compared to the control or 1% minoxidil-treated group. Conclusion These results suggest that T. orientalis extract promotes hair growth by inducing the anagen phase in resting hair follicles and might therefore be a potential hair growth-promoting agent. PMID:23305186

Hair Follicle Miniaturization in a Woolly Hair Nevus: A Novel "Root" Perspective for a Mosaic Hair Disorder.

PubMed

Veraitch, Ophelia; Perez, Alfonso; Hoque, Shamali R; Vizcay-Barrena, Gema; Fleck, Roland A; Fenton, David A; Stefanato, Catherine M

2016-03-01

Woolly hair nevus is a mosaic disorder characterized by unruly, tightly curled hair in a circumscribed area of the scalp. This condition may be associated with epidermal nevi. We describe an 11-year-old boy who initially presented with multiple patches of woolly hair and with epidermal nevi on his left cheek and back. He had no nail, teeth, eye, or cardiac abnormalities. Analysis of plucked hairs from patches of woolly hair showed twisting of the hair shaft and an abnormal hair cuticle. Histopathology of a woolly hair patch showed diffuse hair follicle miniaturization with increased vellus hairs.

Fluorine-induced apoptosis and lipid peroxidation in human hair follicles in vitro.

PubMed

Wang, Zheng-hui; Li, Xiao-li; Yang, Zhuang-qun; Xu, Min

2010-12-01

Fluoride is an essential trace element for human body; however, exposure to high amounts of fluoride has been documented to be correlated with an increasing risk of hair loss. To date, little is known about the mechanism(s) of how fluoride affects hair follicles. Here, we demonstrated that middle (1.0 mmol/L) and high (10.0 mmol/L) concentrations of sodium fluoride (NaF) significantly inhibited hair follicle elongation in vitro, but low NaF (0.1 mmol/L) showed little influence. Moreover, treatment with high levels of NaF resulted in a marked increase in terminal dUTP nick end labeling-positive cells in the outer layer of the outer root sheath, the dermal sheath, and the lower bulb matrix surrounding dermal papilla. Furthermore, the enhanced apoptosis was coupled with an increased oxidative stress manifested as higher malondialdehyde content. Additionally, the presence of selenium considerably antagonized the effects of middle NaF on hair follicles, with regard to either the suppression of hair growth or the induction of oxidative stress and apoptosis. In conclusion, exposure to high levels of fluoride compromises hair follicle growth and accelerate cell apoptosis in vitro. The toxicity of fluoride can be reduced by selenium, at least partially via the suppression of intracellular oxidative stress.

Activating β-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity

PubMed Central

Zhou, Linli; Yang, Kun; Xu, Mingang; Andl, Thomas; Millar, Sarah; Boyce, Steven; Zhang, Yuhang

2016-01-01

Bioengineering hair follicles using cells isolated from human tissue remains as a difficult task. Dermal papilla (DP) cells are known to guide the growth and cycling activities of hair follicles by interacting with keratinocytes. However, DP cells quickly lose their inductivity during in vitro passaging. Rodent DP cell cultures need external addition of chemical factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a small subpopulation of DP cells that are capable of inducing hair follicle formation in vivo. We report here that expression of a stabilized form of β-catenin promoted clonal growth of CD133-positive (CD133+) DP cells in in vitro three-dimensional hydrogel culture while maintaining expression of DP markers, including alkaline phosphatase (AP), CD133, and Integrin α8. After a two-week in vitro culture, cultured CD133+ DP cells with up-regulated β-catenin activity led to an accelerated in vivo hair growth in reconstituted skin than control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was upregulated in CD133+ DP cells. Our data highlight an important role for β-catenin signaling in promoting the inductive capability of CD133+ DP cells for in vitro expansion and in vivo hair follicle regeneration, which could potentially be applied to cultured human DP cells. PMID:27312243

Cuttlefish Ink Melanin Encapsulated in Nanolipid Bubbles and Applied Through a Micro-Needling Procedure Easily Stains White Hair Facilitating Photoepilation.

PubMed

Trelles, Mario A; Almudever, Patricia; Alcolea, Justo M; Cortijo, Julio; Serrano, Gabriel; Expósito, Inmaculada; Royo, Josefina; Leclère, Franck Marie

2016-05-01

Photothermolysis of unwanted hair depends on the presence of melanin in the hair follicle as the chromophore, but is not effective in patients with non-pigmented, melanin-sparse hair shafts and follicles. This split-scalp, double-blind study was to monitor the efficacy of melanin bound in nanosomes to inject exogenous melanin into the hair follicles thus potentiating successful photothermolysis.
Twelve patients, phototypes II-III, with white or very fair hair, were treated with a compound containing melanin encapsulated in nanosomes (Melaser^®) together with a fluorescent marker. Two equal 6 cm² areas were marked on each side of the occiput of the subjects. The compound was applied to a randomly selected experimental side on each patient (area A), and a saline solution applied in the same manner to the contralateral control side (area B). Penetration of the melanin into the hair follicle was assessed using optical and fluorescence microscopy. Also, condition of hair structure was checked in vivo after standard laser settings used for epilation.
A slight transient erythema was observed in those areas where the compound was applied with some perifollicular edema. No such effects were noticed in those areas where saline solution was applied. No persistent complications such as scarring, hypo- or hyperpigmentation were observed in any of the experimental or control areas. Under fluorescence microscopy, the hair structures in the areas to which the compound had been applied showed a clear melanin deposit confirmed by the immunofluorescence intensity, which was highest at 2 hours after application. By optical microscopy, external melanin was deposited in hair follicles. Tests with standard settings for epilation were efficacious in damaging melanin-marked white hair.
This study strongly suggests the safety and efficacy of the application of nanosomes encapsulating melanin for the introduction of melanin into hair follicles. Changes noticed in the hair structure compromising its viability indicated potential application of this external melanin marker for white hair photoepilation.

J Drugs Dermatol. 2016;15(5):615-625.

Structural and Functional Analysis of Intact Hair Follicles and Pilosebaceous Units by Volumetric Multispectral Optoacoustic Tomography.

PubMed

Ford, Steven J; Bigliardi, Paul L; Sardella, Thomas C P; Urich, Alexander; Burton, Neal C; Kacprowicz, Marcin; Bigliardi, Mei; Olivo, Malini; Razansky, Daniel

2016-04-01

Visualizing anatomical and functional features of hair follicle development in their unperturbed environment is key in understanding complex mechanisms of hair pathophysiology and in discovery of novel therapies. Of particular interest is in vivo visualization of the intact pilosebaceous unit, vascularization of the hair bulb, and evaluation of the hair cycle, particularly in humans. Furthermore, noninvasive visualization of the sebaceous glands could offer crucial insight into the pathophysiology of follicle-related diseases and dry or seborrheic skin, in particular by combining in vivo imaging with other phenotyping, genotyping, and microbial analyses. The available imaging techniques are limited in their ability for deep tissue in vivo imaging of hair follicles and lipid-rich sebaceous glands in their entirety without biopsy. We developed a noninvasive, painless, and risk-free volumetric multispectral optoacoustic tomography method for deep tissue three-dimensional visualization of whole hair follicles and surrounding structures with high spatial resolution below 80 μm. Herein we demonstrate on-the-fly assessment of key morphometric parameters of follicles and lipid content as well as functional oxygenation parameters of the associated capillary bed. The ease of handheld operation and versatility of the newly developed approach poise it as an indispensable tool for early diagnosis of disorders of the pilosebaceous unit and surrounding structures, and for monitoring the efficacy of cosmetic and therapeutic interventions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

6-Gingerol inhibits hair cycle via induction of MMP2 and MMP9 expression.

PubMed

Hou, Chun; Miao, Yong; Ji, Hang; Wang, Susheng; Liang, Gang; Zhang, Zhihua; Hong, Weijin

2017-01-01

6-Gingerol is the major active constituent of ginger. In the current study, we aimed to investigate the mechanisms underlying the effects of 6-Gingerol on hair growth. Mice were randomly divided into five groups; after hair depilation (day 0), mice were treated with saline, or different concentrations of 6-Gingerol for 11 days. The histomorphological characteristics of the growing hair follicles were examined after hematoxylin and eosin staining. The results indicated that 6-Gingerol significantly suppressed hair growth compared with that in the control group. And choose the concentration of 6-Gingerol at 1 mg/mL to treated with mice. Moreover, 6-Gingerol (1 mg/mL) significantly reduced hair re-growth ratio, hair follicle number, and hair follicle length, which were associated with increased expression of MMP2 and MMP9. Furthermore, the growth factors, such as EGF, KGF, VEGF, IGF-1 and TGF-β participate in the hair follicle cycle regulation and regulate hair growth. We then measured the concentrations of them using ELISA assays, and the results showed that 6-Gingerol decreased EGF, KGF, VEGF, and IGF-1 concentrations, and increased TGF-β concentration. Thus, this study showed that 6-Gingerol might act as a hair growth suppressive drug via induction of MMP2 and MMP9 expression, which could interfere with the hair cycle.

Differential effect of testosterone on pigmented spot, sebaceous glands and hair follicles in the Syrian hamster flank organ.

PubMed

Wuest, P A; Lucky, A W

1989-01-01

The androgen-dependent flank organ of the Golden Syrian hamster has been used as a model for acne and hair growth. 1-cm silastic capsules of testosterone (T) were implanted subcutaneously into female hamsters. Serum levels of T remained relatively constant after 1 week. Maximum growth of the pigmented spot occurred at 4 weeks but regressed by 6 weeks. In contrast, the growth of the pilosebaceous unit continued for 6 weeks. Total sebaceous area and number of sebaceous lobules increased by 3 weeks with a further increase in total area by 6 weeks. The distribution of lobule size shifted to more large lobules. Diameters of hair follicles increased at 3 and 6 weeks with a concomitant recruitment to large follicles. The density of hairs remained constant. The diminution in size of the pigmented spot between 4 and 6 weeks of T stimulation was not related to a reduction in serum T. In fact, there was persistent growth of the sebaceous glands and hair follicles at this time. The measurement of the pigmented spot of the flank organ is not a reliable indicator of the androgen responsiveness of sebaceous glands and/or hair follicles.

Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

PubMed Central

Higgins, Claire A.; Chen, James C.; Cerise, Jane E.; Jahoda, Colin A. B.; Christiano, Angela M.

2013-01-01

De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

Stem cell dynamics in the hair follicle niche

PubMed Central

Rompolas, Panteleimon; Greco, Valentina

2014-01-01

Hair follicles are skin appendages of the mammalian skin that have the ability to periodically and stereotypically regenerate in order to continuously produce new hair over our lifetime. The ability of the hair follicle to regenerate is due to the presence of stem cells that along with other cell populations and non-cellular components, including molecular signals and extracellular material, make up a niche microenvironment. Mounting evidence suggests that the niche is critical for regulating stem cell behavior and thus the process of regeneration. Here we review the literature concerning past and current studies that have utilized mouse genetic models, combined with other approaches to dissect the molecular and cellular composition of the hair follicle niche. We also discuss our current understanding of how stem cells operate within the niche during the process of tissue regeneration and the factors that regulate their behavior. PMID:24361866

Further Clinical Evidence for the Effect of IGF-1 on Hair Growth and Alopecia.

PubMed

Trüeb, Ralph M

2018-04-01

Observations on the Laron syndrome originally offered the opportunity to explore the effect of insulin-like growth factor 1 (IGF-1) deficiency on human hair growth and differentiation. According to its expression in the dermal hair papilla, IGF-1 is likely involved in reciprocal signaling. It has been shown to affect follicular proliferation, tissue remodeling, and the hair growth cycle, as well as follicular differentiation, identifying IGF-1 signaling as an important mitogenic and morphogenetic regulator in hair follicle biology. Of all the cytokines or growth factors that have been postulated to play a role in hair follicles, ultimately IGF-1 is known to be regulated by androgens. Accordingly, dermal papillary cells from balding scalp follicles were found to secrete significantly less IGF-1 than their counterparts from nonbalding scalp follicles. Herein, hypotrichosis in primary growth hormone deficiency, and a lack of response of female and male androgenetic-type alopecia to treatment with topical minoxidil and oral finasteride in patients who had undergone surgical resection of the pituitary gland, provide further evidence for an effect of IGF-1 on hair growth and alopecia.

Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses

PubMed Central

Imsland, Freyja; McGowan, Kelly; Rubin, Carl-Johan; Henegar, Corneliu; Sundström, Elisabeth; Berglund, Jonas; Schwochow, Doreen; Gustafson, Ulla; Imsland, Páll; Lindblad-Toh, Kerstin; Lindgren, Gabriella; Mikko, Sofia; Millon, Lee; Wade, Claire; Schubert, Mikkel; Orlando, Ludovic; Penedo, Maria Cecilia T; Barsh, Gregory S; Andersson, Leif

2016-01-01

Dun is a wild-type coat color in horses characterized by pigment dilution with a striking pattern of dark areas termed primitive markings. Here we show that pigment dilution in Dun horses is due to radially asymmetric deposition of pigment in the growing hair caused by localized expression of the T-box 3 (TBX3) transcription factor in hair follicles, which in turn determines the distribution of hair follicle melanocytes. Most domestic horses are non-dun, a more intensely pigmented phenotype caused by regulatory mutations impairing TBX3 expression in the hair follicle, resulting in a more circumferential distribution of melanocytes and pigment granules in individual hairs. We identified two different alleles (non-dun1 and non-dun2) causing non-dun color. non-dun2 is a recently derived allele, whereas the Dun and non-dun1 alleles are found in ancient horse DNA, demonstrating that this polymorphism predates horse domestication. These findings uncover a new developmental role for T-box genes and new aspects of hair follicle biology and pigmentation. PMID:26691985

Transcriptional profiling in rat hair follicles following simulated Blast insult: a new diagnostic tool for traumatic brain injury.

PubMed

Zhang, Jing; Carnduff, Lisa; Norman, Grant; Josey, Tyson; Wang, Yushan; Sawyer, Thomas W; Martyniuk, Christopher J; Langlois, Valerie S

2014-01-01

With wide adoption of explosive-dependent weaponry during military activities, Blast-induced neurotrauma (BINT)-induced traumatic brain injury (TBI) has become a significant medical issue. Therefore, a robust and accessible biomarker system is in demand for effective and efficient TBI diagnosis. Such systems will also be beneficial to studies of TBI pathology. Here we propose the mammalian hair follicles as a potential candidate. An Advanced Blast Simulator (ABS) was developed to generate shock waves simulating traumatic conditions on brains of rat model. Microarray analysis was performed in hair follicles to identify the gene expression profiles that are associated with shock waves. Gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) were used to identify cell processes and molecular signaling cascades affected by simulated bomb blasts. Enrichment analyses indicated that genes with altered expression levels were involved in central nervous system (CNS)/peripheral nervous system (PNS) responses as well as signal transduction including Ca2+, K+-transportation-dependent signaling, Toll-Like Receptor (TLR) signaling and Mitogen Activated Protein Kinase (MAPK) signaling cascades. Many of the pathways identified as affected by shock waves in the hair follicles have been previously reported to be TBI responsive in other organs such as brain and blood. The results suggest that the hair follicle has some common TBI responsive molecular signatures to other tissues. Moreover, various TBI-associated diseases were identified as preferentially affected using a gene network approach, indicating that the hair follicle may be capable of reflecting comprehensive responses to TBI conditions. Accordingly, the present study demonstrates that the hair follicle is a potentially viable system for rapid and non-invasive TBI diagnosis.

Transcriptional Profiling in Rat Hair Follicles following Simulated Blast Insult: A New Diagnostic Tool for Traumatic Brain Injury

PubMed Central

Zhang, Jing; Carnduff, Lisa; Norman, Grant; Josey, Tyson; Wang, Yushan; Sawyer, Thomas W.; Martyniuk, Christopher J.; Langlois, Valerie S.

2014-01-01

With wide adoption of explosive-dependent weaponry during military activities, Blast-induced neurotrauma (BINT)-induced traumatic brain injury (TBI) has become a significant medical issue. Therefore, a robust and accessible biomarker system is in demand for effective and efficient TBI diagnosis. Such systems will also be beneficial to studies of TBI pathology. Here we propose the mammalian hair follicles as a potential candidate. An Advanced Blast Simulator (ABS) was developed to generate shock waves simulating traumatic conditions on brains of rat model. Microarray analysis was performed in hair follicles to identify the gene expression profiles that are associated with shock waves. Gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) were used to identify cell processes and molecular signaling cascades affected by simulated bomb blasts. Enrichment analyses indicated that genes with altered expression levels were involved in central nervous system (CNS)/peripheral nervous system (PNS) responses as well as signal transduction including Ca2+, K+-transportation-dependent signaling, Toll-Like Receptor (TLR) signaling and Mitogen Activated Protein Kinase (MAPK) signaling cascades. Many of the pathways identified as affected by shock waves in the hair follicles have been previously reported to be TBI responsive in other organs such as brain and blood. The results suggest that the hair follicle has some common TBI responsive molecular signatures to other tissues. Moreover, various TBI-associated diseases were identified as preferentially affected using a gene network approach, indicating that the hair follicle may be capable of reflecting comprehensive responses to TBI conditions. Accordingly, the present study demonstrates that the hair follicle is a potentially viable system for rapid and non-invasive TBI diagnosis. PMID:25136963

Morphometry of human terminal and vellus hair follicles.

PubMed

Vogt, Annika; Hadam, Sabrina; Heiderhoff, Marc; Audring, Heike; Lademann, Juergen; Sterry, Wolfram; Blume-Peytavi, Ulrike

2007-11-01

Previous studies suggest that drug delivery systems based on particles can be used to deposit active compounds in hair follicles and to target hair follicle-associated cell populations. The development of application protocols is complicated by the fact that there is no information available on the size and the position of key target structures in the different hair follicle types and their intra- and interindividual variation. Therefore, we performed morphometric measurements on histological sections of human terminal (THF) and vellus hair follicles (VHF) from the scalp and the retroauricular region. With 3864 +/- 605 microm and 580 +/- 84 microm in THF compared to 646 +/- 140 microm and 225 +/- 34 microm in VHF, the total length and the length of the infundibulum differed significantly as determined by paired t-test (P < 0.0001). The same level of significance was observed for the position and the length of the bulge region. The thickness of the epithelial lining was lowest in VHF (45 +/- 14 microm at 100 microm from skin surface) compared to 65 +/- 20 microm at 150 microm in THF, while the thickness of the interfollicular epidermis ranged between 64 +/- 12 microm and 99 +/- 18 microm in VHF-bearing skin and 72 +/- 16 microm and 136 +/- 37 microm in THF-bearing skin. In addition, the diameter of the hair follicle opening was determined at 50 microm intervals from the skin surface. Our data suggest that hair follicle types in defined body regions represent rather homogenous groups and that particle-based drug delivery may be a feasible approach, also in larger numbers of individuals. We provide precise information on the size and the position of key target structures in VHF and THF.

Intelligent Image Analysis for Image-Guided Laser Hair Removal and Skin Therapy

NASA Technical Reports Server (NTRS)

Walker, Brian; Lu, Thomas; Chao, Tien-Hsin

2012-01-01

We present the development of advanced automatic target recognition (ATR) algorithms for the hair follicles identification in digital skin images to accurately direct the laser beam to remove the hair. The ATR system first performs a wavelet filtering to enhance the contrast of the hair features in the image. The system then extracts the unique features of the targets and sends the features to an Adaboost based classifier for training and recognition operations. The ATR system automatically classifies the hair, moles, or other skin lesion and provides the accurate coordinates of the intended hair follicle locations. The coordinates can be used to guide a scanning laser to focus energy only on the hair follicles. The intended benefit would be to protect the skin from unwanted laser exposure and to provide more effective skin therapy.

[Prevalence of human papillomavirus in the pubic hair follicles of healthy men and male patients with genital warts].

PubMed

Wang, You-bao; Han, Tao; Zhao, Chun-xiong

2010-09-01

Human papillomavirus (HPV) commonly exists in healthy individuals, but its prevalence in the pubic hair follicles is not yet clear, nor is the relationship between HPV infection in the pubic hair follicles and the recurrence of genital warts in men. This study aimed to investigate HPV infection in the pubic hair follicles of healthy men and patients with genital warts, and to look into the correlation of HPV infection with recurrent genital warts. We included in this study 122 healthy men aged 21-80 years and 86 male patients with genital warts aged 24-61 years, detected HPV in their pubic hair follicles by PCR, and made comparative analysis of the data obtained from the two groups. The positive rate of HPV in the pubic hair follicles of the healthy males was 17.21% (21/122), including 15 cases of HPV6, 4 HPV11, 1 non-HPV6/11 and 1 the mixed type (both HPV6 and HPV11), while that of the genital wart patients was 32.55% (28/86), including 17 cases of HPV6, 7 HPV11, 2 non-HPV6/11 and 2 the mixed type. The incidence of HPV infection is higher in patients with genital warts than in healthy men, while the types of HPV involved are basically the same in the two groups, mainly HPV6 and HPV11.

GENE EXPRESSION IN HEAD HAIR FOLLICLES PLUCKED FROM MEN AND WOMEN

EPA Science Inventory

Characterizing gene expression in hair follicles can help to elucidate the hair growth cycle by delineating the genes and pathways involved in follicular growth and degeneration. The objectives of this study were to determine whether intact RNA could be extracted from a small num...

Hair Follicle Bulb as a Biodosimeter for Low-Level VX Vapor Exposure: Initial Studies Validating the Presence of Potential Protein Biomarkers of Exposure in the Sprague-Dawley Rat Whisker Follicle

DTIC Science & Technology

2006-10-01

lead to false positive segmental hair analysis results.13 Due to the increased risk of false positives associated with segmental hair analysis ...to 200 mg of hair (to allow confirmation testing). 7 The segments are typically washed to remove external contaminants and the chemicals in the hair ...further confirmation. The method overcomes the false positives associated with traditional segmental hair analysis such. By measuring the

Ultrastructure study of hair damage after ultraviolet irradiation.

PubMed

Zuel-Fakkar, Nehal Mohamed; El Khateeb, Ekramy Ahmed; Cousha, Hala Sobhi; Hamed, Dina Mohamed

2013-12-01

Natural ultraviolet exposure induces hair damage, which is difficult to avoid. Most of the research work is focused on the effect of ultraviolet on the epidermis, dermis as well as the immune system, whereas the long-term effect of ultraviolet on hair has not been investigated. we performed our experiment to find out the changes induced in hair follicle and shaft in those patients exposed to high doses of ultraviolet (A and B) during treatment of other skin conditions. Light and transmission electron microscopy examination of scalp hair follicles and shafts of 10 patients with vitiligo under psoralen plus ultraviolet A (group 1) and 10 patients with vitiligo under narrow band ultraviolet B (group 2) was carried out and compared with those of 10 healthy volunteers (group 3). Physical changes in the appearance of hair were more in groups 1 and 2 than control. Reduced hair follicle thickness and perifollicular infiltrate and hyaline disorganized perifollicular collagen were observed more in group 1 than in group 2 with the absence of these changes in group 3. Transmission electron microscopy showed nonspecific cell injury in hair follicles in group 1 more than the other 2 groups, while the damaging effect on hair was more in the second group than the others. Due to the damaging effect of ultraviolet on hair, patients under treatment with this modality should be cautious to protect their hair during treatment. © 2013 Wiley Periodicals, Inc.

HAIR FOLLICLE CHARACTERISTICS AS EARLY MARKER OF TYPE 2 DIABETES

PubMed Central

Miranda, J. Jaime; Taype-Rondan, Alvaro; Tapia, Jose Carlos; Gastanadui-Gonzalez, Maria Gabriela; Roman-Carpio, Ricardo

2016-01-01

Type 2 Diabetes mellitus (DM2) includes a continuum of metabolic disorders characterized by hyperglycemia that causes several chronic long-term complications such as coronary artery disease, peripheral arterial disease, nephropathy, and neuropathy. The hair follicle could reveal signs of early vascular impairment, yet its relationship to early metabolic injuries has been largely ignored. We propose that in earlier stages of the continuum of DM2-related metabolic disorders, a group of susceptible patients who do not yet meet the diagnostic criteria to be considered as persons with DM2 may present chronic vascular impairment and end organ damage, including hair follicle damage, which can be evaluated to identify an early risk marker. This hypothesis is based in the association found between insulin resistance and alopecia in non-diabetic persons, and the hair loss on the lower limbs as a manifestation of long-term peripheral arterial disease among subjects with DM2. In order to test this hypothesis, studies are required to evaluate if hair follicle characteristics are related to and can predict hyperglycemic complications, and if they do so, which feature of the hair follicle, such as hair growth, best characterizes such DM2-related conditions. If this hypothesis were proven to be true, significant advances towards a personalized approach for early prevention strategies and management of DM2 would be made. By focusing on the hair follicles, early stages of metabolic-related organ damage could be identified using non-invasive low-cost techniques. In so doing, this approach could provide early identification of DM2-susceptible individuals and lead to the early initiation of adequate primary prevention strategies to reduce or avoid the onset of large internal organ damage. PMID:27692164

Hair follicle characteristics as early marker of Type 2 Diabetes.

PubMed

Miranda, J Jaime; Taype-Rondan, Alvaro; Tapia, Jose Carlos; Gastanadui-Gonzalez, Maria Gabriela; Roman-Carpio, Ricardo

2016-10-01

Type 2 Diabetes mellitus (DM2) includes a continuum of metabolic disorders characterized by hyperglycemia that causes several chronic long-term complications such as coronary artery disease, peripheral arterial disease, nephropathy, and neuropathy. The hair follicle could reveal signs of early vascular impairment, yet its relationship to early metabolic injuries has been largely ignored. We propose that in earlier stages of the continuum of DM2-related metabolic disorders, a group of susceptible patients who do not yet meet the diagnostic criteria to be considered as persons with DM2 may present chronic vascular impairment and end organ damage, including hair follicle damage, which can be evaluated to identify an early risk marker. This hypothesis is based in the association found between insulin resistance and alopecia in non-diabetic persons, and the hair loss on the lower limbs as a manifestation of long-term peripheral arterial disease among subjects with DM2. In order to test this hypothesis, studies are required to evaluate if hair follicle characteristics are related to and can predict hyperglycemic complications, and if they do so, which feature of the hair follicle, such as hair growth, best characterizes such DM2-related conditions. If this hypothesis were proven to be true, significant advances towards a personalized approach for early prevention strategies and management of DM2 would be made. By focusing on the hair follicles, early stages of metabolic-related organ damage could be identified using non-invasive low-cost techniques. In so doing, this approach could provide early identification of DM2-susceptible individuals and lead to the early initiation of adequate primary prevention strategies to reduce or avoid the onset of large internal organ damage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Boils

MedlinePlus

... boil is an infection that affects groups of hair follicles and nearby skin tissue. Related conditions include: Carbunculosis ... found on the skin's surface. Damage to the hair follicle allows the infection to grow deeper into the ...

Lack of Collagen VI Promotes Wound-Induced Hair Growth.

PubMed

Chen, Peiwen; Cescon, Matilde; Bonaldo, Paolo

2015-10-01

Collagen VI is an extracellular matrix molecule that is abundantly expressed in the skin. However, the role of collagen VI in hair follicle growth is unknown. Here, we show that collagen VI is strongly deposited in hair follicles, and is markedly upregulated by skin wounding. Lack of collagen VI in Col6a1(-/-) mice delays hair cycling and growth under physiological conditions, but promotes wound-induced hair regrowth without affecting skin regeneration. Conversely, addition of purified collagen VI rescues the abnormal wound-induced hair regrowth in Col6a1(-/-) mice. Mechanistic studies revealed that the increased wound-induced hair regrowth of Col6a1(-/-) mice is triggered by activation of the Wnt/β-catenin signaling pathway, and is abolished by inhibition of this pathway. These findings highlight the essential relationships between extracellular matrix (ECM) and hair follicle regeneration, and suggest that collagen VI could be a potential therapeutic target for hair loss and other skin-related diseases.

FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential

PubMed Central

Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

2016-01-01

Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin–mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis. PMID:26912458

Tissue-engineered skin preserving the potential of epithelial cells to differentiate into hair after grafting.

PubMed

Larouche, Danielle; Cuffley, Kristine; Paquet, Claudie; Germain, Lucie

2011-03-01

The aim of this study was to evaluate whether tissue-engineered skin produced in vitro was able to sustain growth of hair follicles in vitro and after grafting. Different tissues were designed. Dissociated newborn mouse keratinocytes or newborn mouse hair buds (HBs) were added onto dermal constructs consisting of a tissue-engineered cell-derived matrix elaborated from either newborn mouse or adult human fibroblasts cultured with ascorbic acid. After 7-21 days of maturation at the air-liquid interface, no hair was noticed in vitro. Epidermal differentiation was observed in all tissue-engineered skin. However, human fibroblast-derived tissue-engineered dermis (hD) promoted a thicker epidermis than mouse fibroblast-derived tissue-engineered dermis (mD). In association with mD, HBs developed epithelial cyst-like inclusions presenting outer root sheath-like attributes. In contrast, epidermoid cyst-like inclusions lined by a stratified squamous epithelium were present in tissues composed of HBs and hD. After grafting, pilo-sebaceous units formed and hair grew in skin elaborated from HBs cultured 10-26 days submerged in culture medium in association with mD. However, the number of normal hair follicles decreased with longer culture time. This hair-forming capacity after grafting was not observed in tissues composed of hD overlaid with HBs. These results demonstrate that epithelial stem cells can be kept in vitro in a permissive tissue-engineered dermal environment without losing their potential to induce hair growth after grafting.

[Effects of Huoxue Bushen Mixture on skin blood vessel neogenesis and vascular endothelial growth factor expression in hair follicle of C57BL/6 mice].

PubMed

Gao, Shang-pu; Huang, Lan; Yang, Xin-wei

2007-03-01

To investigate the possible stimulating mechanism of Huoxue Bushen Mixture (HXBSM), a traditional Chinese compound medicine, on hair growth of mice via measuring the variance of skin blood vessel neogenesis and vascular endothelial growth factor (VEGF) expression in the hair follicle. Hot rosin and paraffin mixture depilation were used to induce C57BL/6 mice hair follicle to enter from telogen into anagen. Ninety C57BL/6 mice were divided into 3 groups randomly: HXBSM group, Yangxue Shengfa Capsule (YXSFC, another traditional Chinese compound medicine) group and untreated group. The mice were fed with corresponding drugs after modeling. The hair growth of the mice was observed every day. Every ten mice out of each group were executed respectively at day 4, 11 and day 17. Skin blood vessel neogenesis was counted through pathological section and VEGF expression in the hair follicle was measured via immunohistochemical method. The number of local blood vessel neogenisis in the HXBSM group observed was larger than that in the untreated group at day 4 (P<0.05); and evidently larger than that in the YXSFC group and the untreated group at day 11 (P<0.05). The expression of VEGF in the hair follicle was distinctively higher than that in the YXSFC group and the untreated group at day 11 and day 17 (P<0.05). HXBSM up-regulates VEGF expression to accelerate blood vessel neogenesis and hair growth.

Dynamic Wnt5a expression in murine hair follicle cycle and its inhibitory effects on follicular.

PubMed

Fang, De-Ren; Lv, Zhong-Fa; Qiao, Gang

2014-04-01

To analyze the dynamic expression of Wnt family member 5A (Wingless-type MMTV integration Wnt site family, member 5a) in murine hair cycle and its inhibitory effects on follicle in vivo. Situ hybridization in full-thickness skin was used to observe the change of mouse protein expression in different growth stages, and Ad-Wnt5a was injected after defeathering to observe the hair follicle growth in vivo. The Wnt5a mRNA was expressed at birth, and was firstly increased then decreased along with the progress of the hair cycle. It reached the peak in advanced stage of growth cycle (P<0.05). Rhoa and β-catenin expression levels were significantly decreased in three groups. Rac2 expression was significantly up-regulated, and the expression level of Wnt5a, Shh and Frizzled2 was increased, but less significantly than group 2. The expression of Wnt5a mRNA is consistent with change of murine follicle cycle, and has obvious inhibitory effects on the growth of hair follicle in vivo, indicating that it is antagonistic to Wnts pathway and interferes the growth of follicle together. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation.

PubMed

Woo, Hyunju; Lee, Seungjun; Kim, Seungbeom; Park, Deokhoon; Jung, Eunsun

2017-07-01

Hair loss known as alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair growth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.

Proanthocyanidins from grape seeds promote proliferation of mouse hair follicle cells in vitro and convert hair cycle in vivo.

PubMed

Takahashi, T; Kamiya, T; Yokoo, Y

1998-11-01

For the purpose of discovering natural products which possess hair growing activity, we examined about 1000 kinds of plant extracts concerning growth-promoting activity with respect to hair follicle cells. After an extensive search, we discovered that proanthocyanidins extracted from grape seeds promote proliferation of hair follicle cells isolated from mice by about 230% relative to controls (100%); and that proanthocyanidins possess remarkable hair-cycle-converting activity from the telogen phase to the anagen phase in C3H mice in vivo test systems. The profile of the active fraction of the proanthocyanidins was elucidated by thiolytic degradation and tannase hydrolysis. We found that the constitutive monomers were epicatechin and catechin; and that the degree of polymerization was 3.5. We demonstrated the possibility of using the proanthocyanidins extracted from grape seeds as agents inducing hair growth.

Collision Tumor between Trichofolliculoma and Melanocytic Nevus.

PubMed

Bolte, Christel; Cullen, Roberto; Sazunic, Ivo

2017-01-01

Trichofolliculoma (TF) is a hamartomatous hair follicle-related tumor, clinically described as a dome-shaped papule with a central pore crossed by one or more silky white hairs. Histologically, it described as a cystic cavity containing keratinous debris, hair shaft fragments, and numerous hair follicles arising from its linings. Collision or compound tumors are a coexistence of two or more identifiable tumors in the same lesion. We present a case of a 47-year-old man with a lesion on his left cheek clinically characterized as a TF. However, the histopathological study reveals a collision tumor involving a TF and a melanocytic nevus. Collision tumors involving melanocytic nevi and hair follicle-related tumors have been previously reported, such as desmoplastic trichoepithelioma, epidermoid cyst, folliculosebaceous cystic hamartoma, and trichoadenoma.

An accessible pharmacodynamic transcriptional biomarker for notch target engagement.

PubMed

Tanis, K Q; Podtelezhnikov, A A; Blackman, S C; Hing, J; Railkar, R A; Lunceford, J; Klappenbach, J A; Wei, B; Harman, A; Camargo, L M; Shah, S; Finney, E M; Hardwick, J S; Loboda, A; Watters, J; Bergstrom, D A; Demuth, T; Herman, G A; Strack, P R; Iannone, R

2016-04-01

γ-Secretase mediates amyloid production in Alzheimer's disease (AD) and oncogenic activity of Notch. γ-Secretase inhibitors (GSIs) are thus of interest for AD and oncology. A peripheral biomarker of Notch activity would aid determination of the therapeutic window and dosing regimen for GSIs, given toxicities associated with chronic Notch inhibition. This study examined the effects of GSI MK-0752 on blood and hair follicle transcriptomes in healthy volunteers. The effects of a structurally diverse GSI on rhesus blood and hair follicles were also compared. Significant dose-related effects of MK-0752 on transcription were observed in hair follicles, but not blood. The GSI biomarker identified in follicles exhibited 100% accuracy in a clinical test cohort, and was regulated in rhesus by a structurally diverse GSI. This study identified a translatable, accessible pharmacodynamic biomarker of GSI target engagement and provides proof of concept of hair follicle RNA as a translatable biomarker source. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model

PubMed Central

Keum, Dong In; Pi, Long-Quan; Hwang, Sungjoo Tommy; Lee, Won-Soo

2015-01-01

Background Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo. Methods We examined whether KRG can prevent premature hair follicle dystrophy in a human hair follicle organ culture model during treatment with a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC). Results 4-HC inhibited human hair growth, induced premature catagen development, and inhibited proliferation and stimulated apoptosis of hair matrix keratinocytes. In addition, 4-HC increased p53 and Bax protein expression and decreased Bcl2 protein expression. Pretreatment with KRG protected against 4-HC-induced hair growth inhibition and premature catagen development. KRG also suppressed 4-HC-induced inhibition of matrix keratinocyte proliferation and stimulation of matrix keratinocyte apoptosis. Moreover, KRG restored 4-HC-induced p53 and Bax/Bcl2 expression. Conclusion Overall, our results indicate that KRG may protect against 4-HC-induced premature catagen development through modulation of p53 and Bax/Bcl2 expression. PMID:27158238

Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model.

PubMed

Keum, Dong In; Pi, Long-Quan; Hwang, Sungjoo Tommy; Lee, Won-Soo

2016-04-01

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo. We examined whether KRG can prevent premature hair follicle dystrophy in a human hair follicle organ culture model during treatment with a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC). 4-HC inhibited human hair growth, induced premature catagen development, and inhibited proliferation and stimulated apoptosis of hair matrix keratinocytes. In addition, 4-HC increased p53 and Bax protein expression and decreased Bcl2 protein expression. Pretreatment with KRG protected against 4-HC-induced hair growth inhibition and premature catagen development. KRG also suppressed 4-HC-induced inhibition of matrix keratinocyte proliferation and stimulation of matrix keratinocyte apoptosis. Moreover, KRG restored 4-HC-induced p53 and Bax/Bcl2 expression. Overall, our results indicate that KRG may protect against 4-HC-induced premature catagen development through modulation of p53 and Bax/Bcl2 expression.

To grow or not to grow: Hair morphogenesis and human genetic hair disorders

PubMed Central

Duverger, Olivier; Morasso, Maria I.

2014-01-01

Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration. PMID:24361867

Low-level laser treatment stimulates hair growth via upregulating Wnt10b and β-catenin expression in C3H/HeJ mice.

PubMed

Zhang, Tiran; Liu, Liqiang; Fan, Jincai; Tian, Jia; Gan, Cheng; Yang, Zengjie; Jiao, Hu; Han, Bing; Liu, Zheng

2017-07-01

This study was conducted in order to evaluate the role of low-level laser treatment (LLLT) in hair growth in C3H/HeJ mice. Healthy C57BL/6 mice were randomly divided into two groups: with and without low-level laser treatment. The skin color of each mouse was observed each day. Skin samples were collected for H&E, immunofluorescence, PCR, and western blot analysis, to observe the morphology of hair follicles and detect the expression levels of Wnt10b and β-catenin. Observation of skin color demonstrated that black pigmentation started significantly earlier in the laser group than in the control group. Hair follicle number in both groups showed no difference; however, the hair follicle length presented a significant difference. Wnt10b protein was detected on the second day in hair matrix cells in the LLLT group but not in the control group. PCR and western blot results both illustrated that expression of Wnt10b and β-catenin was significantly higher in the LLLT group than in the control group. Our study illustrated that low-level laser treatment can promote hair regrowth by inducing anagen phase of hair follicles via initiating the Wnt10b/β-catenin pathway.

Modulatory Role of Sensory Innervation on Hair Follicle Stem Cell Progeny during Wound Healing of the Rat Skin

PubMed Central

Martínez-Martínez, Eduardo; Galván-Hernández, Claudio I.; Toscano-Márquez, Brenda; Gutiérrez-Ospina, Gabriel

2012-01-01

Background The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. Methodology/Principal Findings We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU+) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU+ nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU+/CldU+). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU+/CldU+ cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34+ and BrdU-retaining cells of the hair follicles. Conclusions/Significance Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing. PMID:22574159

Modulatory role of sensory innervation on hair follicle stem cell progeny during wound healing of the rat skin.

PubMed

Martínez-Martínez, Eduardo; Galván-Hernández, Claudio I; Toscano-Márquez, Brenda; Gutiérrez-Ospina, Gabriel

2012-01-01

The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU(+)) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU(+) nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU(+)/CldU(+)). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU(+)/CldU(+) cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34(+) and BrdU-retaining cells of the hair follicles. Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing.

The ciliopathy gene Rpgrip1l is essential for hair follicle development.

PubMed

Chen, Jiang; Laclef, Christine; Moncayo, Alejandra; Snedecor, Elizabeth R; Yang, Ning; Li, Li; Takemaru, Ken-Ichi; Paus, Ralf; Schneider-Maunoury, Sylvie; Clark, Richard A

2015-03-01

The primary cilium is essential for skin morphogenesis through regulating the Notch, Wnt, and hedgehog signaling pathways. Prior studies on the functions of primary cilia in the skin were based on the investigations of genes that are essential for cilium formation. However, none of these ciliogenic genes has been linked to ciliopathy, a group of disorders caused by abnormal formation or function of cilia. To determine whether there is a genetic and molecular link between ciliopathies and skin morphogenesis, we investigated the role of RPGRIP1L, a gene mutated in Joubert (JBTS) and Meckel (MKS) syndromes, two severe forms of ciliopathy, in the context of skin development. We found that RPGRIP1L is essential for hair follicle morphogenesis. Specifically, disrupting the Rpgrip1l gene in mice resulted in reduced proliferation and differentiation of follicular keratinocytes, leading to hair follicle developmental defects. These defects were associated with significantly decreased primary cilium formation and attenuated hedgehog signaling. In contrast, we found that hair follicle induction and polarization and the development of interfollicular epidermis were unaffected. This study indicates that RPGRIP1L, a ciliopathy gene, is essential for hair follicle morphogenesis likely through regulating primary cilia formation and the hedgehog signaling pathway.

Co-option of Hair Follicle Keratins into Amelogenesis Is Associated with the Evolution of Prismatic Enamel: A Hypothesis

PubMed Central

Beniash, Elia

2017-01-01

Recent discovery of hair follicle keratin 75 (KRT75) in enamel raises questions about the function of this protein in enamel and the mechanisms of its secretion. It is also not clear how this protein with a very specific and narrow expression pattern, limited to the inner root sheath of the hair follicle, became associated with enamel. We propose a hypothesis that KRT75 was co-opted by ameloblasts during the evolution of Tomes' process and the prismatic enamel in synapsids. PMID:29114231

Balance between fibroblast growth factor 10 and secreted frizzled-relate protein-1 controls the development of hair follicle by competitively regulating β-catenin signaling.

PubMed

Zhang, Haihua; Nan, Weixiao; Wang, Shiyong; Si, Huazhe; Li, Guangyu

2018-07-01

Growth of hairs depends on the regular development of hair follicles which are hypothesized to be regulated by fibroblast growth factor 10 (FGF10) and secreted frizzled-relate protein-1 (sFRP1). In the current study, the effect of FGF10 or sFRP1 on hair follicle cells was assessed and the possible mechanism mediating the interaction between FGF10 and sFRP1 in hair follicle cells was explored. Out root sheath (ORS) and dermal papilla (DP) cells were isolated from mink skin tissues and subjected to administrations of FGF10 (50 ng/ml) or sFRP1 (10 ng/ml). Then proliferation, cell cycle distribution, and migration potentials of both cell types were detected. Moreover, the nuclear translocation of β-catenin was determined. The results showed that the administration of FGF10 increased cell proliferation and migration potential in both cell types, which was associated with the up-regulated nuclear level of β-catenin. To the contrary, the administration of sFRP1 decreased cell proliferation and migration potentials while induced the G1 cell cycle arrest in both cell types by inhibiting nuclear translocation of β-catenin. Compared with the sole administrations, the co-treatment of FGF10 and sFRP1 had a medium effect on cell proliferation, cell cycle distribution, cell migration, and nuclear β-catenin level, representing an antagonistic interaction between the two factors, which was exerted by competitively regulating β-catenin pathway. Conclusively, the cycle of hair follicles was promoted by FGF10 while blocked by sFRP1 and the interplay between the two factors controlled the development of hair follicles by competitively regulating β-catenin signaling. Copyright © 2018. Published by Elsevier Masson SAS.

Communication network in the follicular papilla and connective tissue sheath through gap junctions in human hair follicles.

PubMed

Iguchi, Makiko; Hara, Masahiro; Manome, Hideaki; Kobayasi, Hiromi; Tagami, Hachiro; Aiba, Setsuya

2003-06-01

Epithelial-mesenchymal interactions play a crucial role in the induction of life-long cyclic transformations of hair follicles. Many studies have already demonstrated several candidates for the soluble factors secreted from the mesenchymal components of the hair follicle, i.e. the follicular papilla (FP) and connective tissue sheath (CTS), which may be responsible for hair cycling. In this paper, we focused on cell-cell contact between FP cells (FPCs), between CTS cells (CTSCs), and between FPCs and CTSCs that may allow these mesenchymal components to function as a syncytium during hair cycling. Electron microscopic examination of the FP and the CTS obtained from human scalp revealed a tri-lamellar structure of the plasma membranes, which is a characteristic of gap junctions at the cell-cell contacting area. The immunohistochemical study with anticonnexin 43 Ab using a confocal laser scanning microscope demonstrated numerous spotted positive signals scattered throughout the FP. In the CTS, spotted positive signals were arranged linearly along the basement membrane of the hair follicle. In particular, these positive spots were aggregated in the transitional region between the FP and the CTS. By Western blot analysis of total protein extracts from the cultured FPCs and neonatal human dermal fibroblasts using anticonnexin 43 antibody, a positive band corresponding to connexin 43 was detected at 43 kDa on both the FPC lane and fibroblast lane. These findings suggest that the FP and the CTS form a communicating network through gap junctions, which may play a role in controlling the dynamic structural changes of hair follicles during hair cycling.

Inhibition of hair follicle growth by a laminin-1 G-domain peptide, RKRLQVQLSIRT, in an organ culture of isolated vibrissa rudiment.

PubMed

Hayashi, Kazuhiro; Mochizuki, Mayumi; Nomizu, Motoyoshi; Uchinuma, Eijyu; Yamashina, Shohei; Kadoya, Yuichi

2002-04-01

We established a serum-free organ culture system of isolated single vibrissa rudiments taken from embryonic day 13 mice. This system allowed us to test more than 30 laminin-derived cell adhesive peptides to determine their roles on the growth and differentiation of vibrissa hair follicles. We found that the RKRLQVQLSIRT sequence (designated AG-73), which mapped to the LG-4 module of the laminin-alpha1 chain carboxyl-terminal G domain, perturbed the growth of hair follicles in vitro. AG-73 is one of the cell-binding peptides identified from more than 600 systematically synthesized 12 amino acid peptides covering the whole amino acid sequence of the laminin-alpha1, -beta1, and -gamma1 chains, by cell adhesion assay. Other cell-adhesive laminin peptides and a control scrambled peptide, LQQRRSVLRTKI, however, failed to show any significant effects on the growth of hair follicles. The AG-73 peptide binds to syndecan-1, a transmembrane heparan-sulfate proteoglycan. Syndecan-1 was expressed in both the mesenchymal condensation and the epithelial hair peg of developing vibrissa, suggesting that AG-73 binding to the cell surface syndecan-1 perturbed the epithelial-mesenchymal interactions of developing vibrissa. The formation of hair bulbs was aberrant in the explants treated with AG-73. In addition, impaired basement membrane formation, an abnormal cytoplasmic bleb formation, and an unusual basal formation of actin bundles were noted in the AG-73-treated-hair matrix epithelium, indicating that AG-73 binding perturbs various steps of epithelial morphogenesis, including the basement membrane remodeling. We also found a region-specific loss of the laminin-alpha1 chain in the basement membrane at the distal region of the invading hair follicle epithelium, indicating that laminins play a part in hair morphogenesis.

Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans

PubMed Central

2013-01-01

Background Hair is one of the main distinguishing characteristics of mammals and it has many important biological functions. Cetaceans originated from terrestrial mammals and they have evolved a series of adaptations to aquatic environments, which are of evolutionary significance. However, the molecular mechanisms underlying their aquatic adaptations have not been well explored. This study provided insights into the evolution of hair loss during the transition from land to water by investigating and comparing two essential regulators of hair follicle development and hair follicle cycling, i.e., the Hairless (Hr) and FGF5 genes, in representative cetaceans and their terrestrial relatives. Results The full open reading frame sequences of the Hr and FGF5 genes were characterized in seven cetaceans. The sequence characteristics and evolutionary analyses suggested the functional loss of the Hr gene in cetaceans, which supports the loss of hair during their full adaptation to aquatic habitats. By contrast, positive selection for the FGF5 gene was found in cetaceans where a series of positively selected amino acid residues were identified. Conclusions This is the first study to investigate the molecular basis of the hair loss in cetaceans. Our investigation of Hr and FGF5, two indispensable regulators of the hair cycle, provide some new insights into the molecular basis of hair loss in cetaceans. The results suggest that positive selection for the FGF5 gene might have promoted the termination of hair growth and early entry into the catagen stage of hair follicle cycling. Consequently, the hair follicle cycle was disrupted and the hair was lost completely due to the loss of the Hr gene function in cetaceans. This suggests that cetaceans have evolved an effective and complex mechanism for hair loss. PMID:23394579

Advanced chemical imaging and comparison of human and porcine hair follicles for drug delivery by confocal Raman microscopy.

PubMed

Franzen, Lutz; Mathes, Christiane; Hansen, Steffi; Windbergs, Maike

2013-06-01

Hair follicles have recently gained a lot of interest for dermal drug delivery. They provide facilitated penetration into the skin and a high potential to serve as a drug depot. In this area of research, excised pig ear is a widely accepted in vitro model to evaluate penetration of drug delivery into hair follicles. However, a comparison of human and porcine follicles in terms of chemical composition has not been performed so far. In this study, we applied confocal Raman microscopy as a chemically selective imaging technique to compare human and porcine follicle composition and to visualize component distribution within follicle cross-sections. Based on the evaluation of human and porcine Raman spectra optical similarity for both species was successfully confirmed. Furthermore, cyanoacrylate skin surface biopsies, which are generally used to determine the extent of follicular penetration, were imaged by a novel complementary analytical approach combining confocal Raman microscopy and optical profilometry. This all-encompassing analysis allows investigation of intactness and component distribution of the excised hair bulb in three dimensions. Confocal Raman microscopy shows a high potential as a noninvasive and chemically selective technique for the analysis of trans-follicular drug delivery.

Advanced chemical imaging and comparison of human and porcine hair follicles for drug delivery by confocal Raman microscopy

NASA Astrophysics Data System (ADS)

Franzen, Lutz; Mathes, Christiane; Hansen, Steffi; Windbergs, Maike

2013-06-01

Hair follicles have recently gained a lot of interest for dermal drug delivery. They provide facilitated penetration into the skin and a high potential to serve as a drug depot. In this area of research, excised pig ear is a widely accepted in vitro model to evaluate penetration of drug delivery into hair follicles. However, a comparison of human and porcine follicles in terms of chemical composition has not been performed so far. In this study, we applied confocal Raman microscopy as a chemically selective imaging technique to compare human and porcine follicle composition and to visualize component distribution within follicle cross-sections. Based on the evaluation of human and porcine Raman spectra optical similarity for both species was successfully confirmed. Furthermore, cyanoacrylate skin surface biopsies, which are generally used to determine the extent of follicular penetration, were imaged by a novel complementary analytical approach combining confocal Raman microscopy and optical profilometry. This all-encompassing analysis allows investigation of intactness and component distribution of the excised hair bulb in three dimensions. Confocal Raman microscopy shows a high potential as a noninvasive and chemically selective technique for the analysis of trans-follicular drug delivery.

Iontophoresis of minoxidil sulphate loaded microparticles, a strategy for follicular drug targeting?

PubMed

Gelfuso, Guilherme M; Barros, M Angélica de Oliveira; Delgado-Charro, M Begoña; Guy, Richard H; Lopez, Renata F V

2015-10-01

The feasibility of targeting drugs to hair follicles by a combination of microencapsulation and iontophoresis has been evaluated. Minoxidil sulphate (MXS), which is used in the treatment of alopecia, was selected as a relevant drug with respect to follicular penetration. The skin permeation and disposition of MXS encapsulated in chitosan microparticles (MXS-MP) was evaluated in vitro after passive and iontophoretic delivery. Uptake of MXS was quantified at different exposure times in the stratum corneum (SC) and hair follicles. Microencapsulation resulted in increased (6-fold) drug accumulation in the hair follicles relative to delivery from a simple MXS solution. Application of iontophoresis enhanced follicular delivery for both the solution and the microparticle formulations. It appears, therefore, that microencapsulation and iontophoresis can act synergistically to enhance topical drug targeting to hair follicles. Copyright © 2015 Elsevier B.V. All rights reserved.

Noninvasive method for assessing the human circadian clock using hair follicle cells

PubMed Central

Akashi, Makoto; Soma, Haruhiko; Yamamoto, Takuro; Tsugitomi, Asuka; Yamashita, Shiko; Yamamoto, Takuya; Nishida, Eisuke; Yasuda, Akio; Liao, James K.; Node, Koichi

2010-01-01

A thorough understanding of the circadian clock requires qualitative evaluation of circadian clock gene expression. Thus far, no simple and effective method for detecting human clock gene expression has become available. This limitation has greatly hampered our understanding of human circadian rhythm. Here we report a convenient, reliable, and less invasive method for detecting human clock gene expression using biopsy samples of hair follicle cells from the head or chin. We show that the circadian phase of clock gene expression in hair follicle cells accurately reflects that of individual behavioral rhythms, demonstrating that this strategy is appropriate for evaluating the human peripheral circadian clock. Furthermore, using this method, we indicate that rotating shift workers suffer from a serious time lag between circadian gene expression rhythms and lifestyle. Qualitative evaluation of clock gene expression in hair follicle cells, therefore, may be an effective approach for studying the human circadian clock in the clinical setting. PMID:20798039

Vitamin D3 analogs stimulate hair growth in nude mice.

PubMed

Vegesna, Vijaya; O'Kelly, James; Uskokovic, Milan; Said, Jonathan; Lemp, Nathan; Saitoh, Takayuki; Ikezoe, Takayuki; Binderup, Lise; Koeffler, H Phillip

2002-11-01

The active form of vitamin D3 can regulate epidermal keratinization by inducing terminal differentiation; and mice lacking the vitamin D receptor display defects leading to postnatal alopecia. These observations implicate the vitamin D3 pathway in regulation of hair growth. We tested the ability of 1,25 dihydroxyvitamin D3 and its synthetic analogs to stimulate hair growth in biege/nude/xid (BNX) nu/nu (nude) mice exhibiting congenital alopecia. Nude mice were treated with different vitamin D3 analogs at doses that we had previously found to be the highest dose without inducing toxicity (hypercalcemia). The mice were monitored for hair growth and were scored according to a defined scale. Skin samples were taken for histological observation of hair follicles and for extraction of RNA and protein. Vitamin D3 analogs dramatically stimulated the hair growth of nude mice, although parental 1,25 dihydroxyvitamin D3 had no effect. Hair growth occurred in a cyclical pattern, accompanied by formation of normal hair follicles and increased expression of certain keratins (Ha7, Ha8, and Hb3). Vitamin D3 analogs seem to act on keratinocytes to initiate hair follicle cycling and stimulate hair growth in mice that otherwise do not grow hair.

Hair radioactivity as a measure of exposure to radioisotopes

NASA Technical Reports Server (NTRS)

Strain, W. H.; Pories, W. J.; Fratianne, R. B.; Flynn, A.

1972-01-01

Since many radioisotopes accumulate in hair, this tropism was investigated by comparing the radioactivity of shaved with plucked hair collected from rats at various time intervals up to 24 hrs after intravenous injection of the ecologically important radioisotopes, iodine-131, manganese-54, strontium-85, and zinc-65. The plucked hair includes the hair follicles where biochemical transformations are taking place. The data indicate a slight surge of each radioisotpe into the hair immediately after injection, a variation of content of each radionuclide in the hair, and a greater accumulation of radioactivity in plucked than in shaved hair. These results have application not only to hair as a measure of exposure to radioisotopes, but also to tissue damage and repair at the hair follicle.

To grow or not to grow: hair morphogenesis and human genetic hair disorders.

PubMed

Duverger, Olivier; Morasso, Maria I

2014-01-01

Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration. Published by Elsevier Ltd.

1α,25-dihydroxyvitamin D3 modulates the hair-inductive capacity of dermal papilla cells: therapeutic potential for hair regeneration.

PubMed

Aoi, Noriyuki; Inoue, Keita; Chikanishi, Toshihiro; Fujiki, Ryoji; Yamamoto, Hanako; Kato, Harunosuke; Eto, Hitomi; Doi, Kentaro; Itami, Satoshi; Kato, Shigeaki; Yoshimura, Kotaro

2012-08-01

Dermal papilla cells (DPCs) have the potential to induce differentiation of epithelial stem cells into hair, and Wnt signaling is deeply involved in the initiation process. The functional limitation of expanded adult DPCs has been a difficult challenge for cell-based hair regrowth therapy. We previously reported that 1α,25-dihydroxyvitamin D(3) (VD(3)) upregulates expression of transforming growth factor (TGF)-β2 and alkaline phosphatase (ALP) activity, both features of hair-inducing human DPCs (hDPCs). In this study, we further examined the effects and signaling pathways associated with VD(3) actions on DPCs. VD(3) suppressed hDPC proliferation in a dose-dependent, noncytotoxic manner. Among the Wnt-related genes investigated, Wnt10b expression was significantly upregulated by VD(3) in hDPCs. Wnt10b upregulation, as well as upregulation of ALPL (ALP, liver/bone/kidney) and TGF-β2, by VD(3) was specific in hDPCs and not detected in human dermal fibroblasts. Screening of paracrine or endocrine factors in the skin indicated that all-trans retinoic acid (atRA) upregulated Wnt10b gene expression, although synergistic upregulation (combined atRA and VD(3)) was not seen. RNA interference with vitamin D receptor (VDR) revealed that VD(3) upregulation of Wnt10b, ALPL, and TGF-β2 was mediated through the genomic VDR pathway. In a rat model of de novo hair regeneration by murine DPC transplantation, pretreatment with VD(3) significantly enhanced hair folliculogenesis. Specifically, a greater number of outgrowing hair shafts and higher maturation of regenerated follicles were observed. Together, these data suggest that VD(3) may promote functional differentiation of DPCs and be useful in preserving the hair follicle-inductive capacity of cultured DPCs for hair regeneration therapies.

Discrimination between basal cell carcinoma and hair follicles in skin tissue sections by Raman micro-spectroscopy

NASA Astrophysics Data System (ADS)

Larraona-Puy, M.; Ghita, A.; Zoladek, A.; Perkins, W.; Varma, S.; Leach, I. H.; Koloydenko, A. A.; Williams, H.; Notingher, I.

2011-05-01

Skin cancer is the most common human malignancy and basal cell carcinoma (BCC) represents approximately 80% of the non-melanoma cases. Current methods of treatment require histopathological evaluation of the tissues by qualified personnel. However, this method is subjective and in some cases BCC can be confused with other structures in healthy skin, including hair follicles. In this preliminary study, we investigated the potential of Raman micro-spectroscopy (RMS) to discriminate between hair follicles and BCC in skin tissue sections excised during Mohs micrographic surgery (MMS). Imaging and diagnosis of skin sections was automatically generated using ' a priori'-built spectral model based on LDA. This model had 90 ± 9% sensitivity and 85 ± 9% specificity for discrimination of BCC from dermis and epidermis. The model used selected Raman bands corresponding to the largest spectral differences between the Raman spectra of BCC and the normal skin regions, associated mainly with nucleic acids and collagen type I. Raman spectra corresponding to the epidermis regions of the hair follicles were found to be closer to those of healthy epidermis rather than BCC. Comparison between Raman spectral images and the gold standard haematoxylin and eosin (H&E) histopathology diagnosis showed good agreement. Some hair follicle regions were misclassified as BCC; regions corresponded mainly to the outermost layer of hair follicle (basal cells) which are expected to have higher nucleic acid concentration. This preliminary study shows the ability of RMS to distinguish between BCC and other tissue structures associated to healthy skin which can be confused with BCC due to their similar morphology.

Arachidonate 12-Lipoxygenase Inhibitors Promote S100A3 Citrullination in Cultured SW480 Cells and Isolated Hair Follicles.

PubMed

Kizawa, Kenji; Fujimori, Takeshi; Kawai, Tomomitsu

2017-01-01

The human hair shaft is covered with multiple scale-like cuticular layers. During the terminal differentiation stage of immature cuticular cells within the hair follicle, cysteine-rich calcium binding S100A3 protein is predominantly translated, and its arginine residues are converted to citrullines by peptidylarginine deiminases (PADI). In this study, we found several naturally occurring compounds (e.g., hinokitiol, escletin, and quercetin) elevate S100A3 citrullination in a human colorectal adenocarcinoma cell line (SW480). Selected compounds similarly promoted cuticular differentiation within isolated human hair follicles. Their promotive activities correlated with the previously reported inhibitory activities of arachidonate 12-lipoxygenase (ALOX12) in vitro. Microarray analysis revealed that ALOX12 inhibitor remarkably up-regulated heparin-binding epidermal growth factor-like growth factor (HBEGF). ALOX12 inhibitor and recombinant HBEGF similarly regulated expression of PADI genes in SW480 cells. In isolated hair follicles, arachidonic acid strongly promoted S100A3 citrullination along with elevation of HBEGF. These results suggest that ALOX12 inhibition efficiently triggers hair cuticle maturation by modulating arachidonate metabolism in concert with HBEGF.

Antimicrobial peptide lysozyme has the potential to promote mouse hair follicle growth in vitro.

PubMed

Su, Yongsheng; Liu, Hui; Wang, Jin; Lin, Bojie; Miao, Yong; Hu, Zhiqi

2015-10-01

Lysozyme is a well-known antimicrobial peptide that exists widely in mammalian skin and it is also expressed by pilosebaceous units. However, the exact location of lysozyme in hair follicles and whether it exerts any direct effects on hair follicle growth are unclear. To determine whether lysozyme affected hair growth in vitro, micro-dissected mouse vibrissae follicles (VFs) were treated in serum-free organ culture for 3 days with lysozyme (1-10μg/ml). After that, the effects of lysozyme on dermal papilla (DP) cells were also investigated. Lysozyme was mainly identified in DP and dermal sheath regions of VF by immunochemistry. In addition, 5-10μg/ml lysozyme had a promoting effect on shaft production. It was also associated with significant proliferation of matrix keratinocytes by immunofluorescence observation. Furthermore, lysozyme promoted hair growth by increasing the levels of alkaline phosphatase and lymphoid enhancer factor 1 in DP, as determined by Western blotting. These results indicate that lysozyme is a promoter of VF growth via enhancing the hair-inductive capacity of DP cells during organ culture. Copyright © 2015 Elsevier GmbH. All rights reserved.

Fibroblast growth factor 5-short (FGF5s) inhibits the activity of FGF5 in primary and secondary hair follicle dermal papilla cells of cashmere goats.

PubMed

He, Xiaolin; Chao, Yuan; Zhou, Guangxian; Chen, Yulin

2016-01-10

To determine the relationship between fibroblast growth factor 5 (FGF5) and FGF5-short (FGF5s) in dermal papilla cells of cashmere goat primary and secondary hair follicles. We isolated dermal papilla cells from primary hair follicle (PHF) and secondary hair follicle (SHF) of cashmere goat, and found that the FGF5 receptor, fibroblast growth factor receptor 1 (FGFR1), was expressed in these two types of dermal papilla cells. Moreover, adenovirus-mediated overexpression of FGF5 could upregulate the mRNA expression of insulin-like growth factor-1 (IGF-1), versican and noggin that were important for follicle growth maintenance, whereas downregulate the expression of anagen chalone bone morphogenetic protein 4 (BMP4) in dermal papilla cells. However, these alterations were partly reversed by FGF5s overexpression. In conclusion, our results demonstrated that FGF5s acted as an inhibitor of FGF5 in the regulation of anagen-catagen transition of cashmere goat dermal papilla cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Sterol intermediates of cholesterol biosynthesis inhibit hair growth and trigger an innate immune response in cicatricial alopecia.

PubMed

Panicker, Sreejith P; Ganguly, Taneeta; Consolo, Mary; Price, Vera; Mirmirani, Paradi; Honda, Kord; Karnik, Pratima

2012-01-01

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders.

Demodex injai: a new species of hair follicle mite (Acari: Demodecidae) from the domestic dog (Canidae).

PubMed

Desch, Clifford E; Hillier, Andrew

2003-03-01

Demondex injai sp. nov. is described from the hair follicles of a domestic dog in Columbus, OH in October 1996. The mites occupy follicles from the orifice down to and into the sebaceous glands. The individual host may harbor both this new species and D. canis. A comparison of these two species is provided for identification purposes.

The histological characteristics, age-related thickness change of skin, and expression of the HSPs in the skin during hair cycle in yak (Bos grunniens)

PubMed Central

Yang, Xue; Cui, Yan; Yue, Jing; He, Honghong; Yu, Chuan; Liu, Penggang; Liu, Jun; Ren, Xiandong; Meng, Yun

2017-01-01

Objective This experiment was conducted to study the histological characteristics, age-related thickness changes, and expression of HSPs in the skin of yak. Methods A total of 20 yaks (10 males and 10 females) were used. Different regions of the normal skin of three different ages (newborn, half-year-old and adult) of yaks were harvested for histological study and thickness measurement. Biopsy samples were taken from the scapula regions of the skin from the same five approximately 1-year-old yaks during the hair cycle (telogen, anagen and catagen). RT-PCR, western blot and immunohistochemistry methods using the mRNA and protein levels were used to detect the expression of HSP27, HSP70 and HSP90. RT-PCR method was used to detect the mRNA expression of CGI-58 and KDF1. The IPP6.0 software was used to analyze the immunohistochemistry and measure the thickness of the skin. Results The general histological structure of hairy yak skin was similar to other domestic mammals. The unique features included prominent cutaneous vascular plexuses, underdeveloped sweat glands, a large number of nasolabial glands in the nasolabial plate, and hair follicle groups composed of one primary follicle and several secondary follicles. The skin, epidermis and dermis thickness did vary significantly between different body regions and different ages. The thickness of the skin, epidermis and dermis increased from newborn to adult in yaks. Yak skin thickness decreased from dorsally to ventrally on the trunk. The skin on the lateral surface was thicker than the skin on the medial surface on the limbs. HSP27, HSP70 and HSP90 showed different expression patterns during the hair cycle using RT-PCR, western blot and immunohistochemistry methods. The expression of HSP27 mRNA and protein in the anagen stage was the highest, followed by the catagen stage, and the expression in the telogen stage was the lowest. The expression of HSP70 mRNA and protein in the telogen stage was the highest, followed by the anagen stage, and the expression in the catagen stage was the lowest. The expression of HSP90 mRNA and protein in the anagen stage was the highest, followed by the telogen stage, and the expression in the catagen stage was the lowest. HSPs were mainly expressed in the outer root sheath of hair follicle during the hair cycle, also expressed in epidermis, sebaceous gland and sweat gland in the skin of Yak. The expression of CGI-58 mRNA in the anagen stage was the highest, followed by the catagen stage, and the expression in the telogen stage was the lowest. The expression of KDF1 mRNA in the telogen stage was the highest, followed by the catagen stage, and the expression in the anagen stage was the lowest. Meaning In this study, we examined and fully described the histology of normal skin in Yak and measured the skin thickness of different ages and different regions in Yak. These data may be useful to better understand and appreciate the adaptability features of yak skin. Our investigation reports the expression patterns of HSPs in yak skin for the first time. The different expression pattern of HSPs during the hair cycle suggests they may play different roles in yak hair follicle biology. PMID:28463974

The histological characteristics, age-related thickness change of skin, and expression of the HSPs in the skin during hair cycle in yak (Bos grunniens).

PubMed

Yang, Xue; Cui, Yan; Yue, Jing; He, Honghong; Yu, Chuan; Liu, Penggang; Liu, Jun; Ren, Xiandong; Meng, Yun

2017-01-01

This experiment was conducted to study the histological characteristics, age-related thickness changes, and expression of HSPs in the skin of yak. A total of 20 yaks (10 males and 10 females) were used. Different regions of the normal skin of three different ages (newborn, half-year-old and adult) of yaks were harvested for histological study and thickness measurement. Biopsy samples were taken from the scapula regions of the skin from the same five approximately 1-year-old yaks during the hair cycle (telogen, anagen and catagen). RT-PCR, western blot and immunohistochemistry methods using the mRNA and protein levels were used to detect the expression of HSP27, HSP70 and HSP90. RT-PCR method was used to detect the mRNA expression of CGI-58 and KDF1. The IPP6.0 software was used to analyze the immunohistochemistry and measure the thickness of the skin. The general histological structure of hairy yak skin was similar to other domestic mammals. The unique features included prominent cutaneous vascular plexuses, underdeveloped sweat glands, a large number of nasolabial glands in the nasolabial plate, and hair follicle groups composed of one primary follicle and several secondary follicles. The skin, epidermis and dermis thickness did vary significantly between different body regions and different ages. The thickness of the skin, epidermis and dermis increased from newborn to adult in yaks. Yak skin thickness decreased from dorsally to ventrally on the trunk. The skin on the lateral surface was thicker than the skin on the medial surface on the limbs. HSP27, HSP70 and HSP90 showed different expression patterns during the hair cycle using RT-PCR, western blot and immunohistochemistry methods. The expression of HSP27 mRNA and protein in the anagen stage was the highest, followed by the catagen stage, and the expression in the telogen stage was the lowest. The expression of HSP70 mRNA and protein in the telogen stage was the highest, followed by the anagen stage, and the expression in the catagen stage was the lowest. The expression of HSP90 mRNA and protein in the anagen stage was the highest, followed by the telogen stage, and the expression in the catagen stage was the lowest. HSPs were mainly expressed in the outer root sheath of hair follicle during the hair cycle, also expressed in epidermis, sebaceous gland and sweat gland in the skin of Yak. The expression of CGI-58 mRNA in the anagen stage was the highest, followed by the catagen stage, and the expression in the telogen stage was the lowest. The expression of KDF1 mRNA in the telogen stage was the highest, followed by the catagen stage, and the expression in the anagen stage was the lowest. In this study, we examined and fully described the histology of normal skin in Yak and measured the skin thickness of different ages and different regions in Yak. These data may be useful to better understand and appreciate the adaptability features of yak skin. Our investigation reports the expression patterns of HSPs in yak skin for the first time. The different expression pattern of HSPs during the hair cycle suggests they may play different roles in yak hair follicle biology.

Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles.

PubMed

Rezza, Amélie; Wang, Zichen; Sennett, Rachel; Qiao, Wenlian; Wang, Dongmei; Heitman, Nicholas; Mok, Ka Wai; Clavel, Carlos; Yi, Rui; Zandstra, Peter; Ma'ayan, Avi; Rendl, Michael

2016-03-29

The hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for SC activation during the adult hair cycle, but signal exchange between niche and SC precursors/transit-amplifying cell (TAC) progenitors that regulates HF morphogenetic growth is largely unknown. Here we use six transgenic reporters to isolate 14 major skin and HF cell populations. With next-generation RNA sequencing, we characterize their transcriptomes and define unique molecular signatures. SC precursors, TACs, and the DP niche express a plethora of ligands and receptors. Signaling interaction network analysis reveals a bird's-eye view of pathways implicated in epithelial-mesenchymal interactions. Using a systematic tissue-wide approach, this work provides a comprehensive platform, linked to an interactive online database, to identify and further explore the SC/TAC/niche crosstalk regulating HF growth. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Role of Arachidonic Acid in Promoting Hair Growth

PubMed Central

Munkhbayar, Semchin; Jang, Sunhyae; Cho, A-Ri; Choi, Soon-Jin; Shin, Chang Yup; Eun, Hee Chul; Kim, Kyu Han

2016-01-01

Background Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid present in all mammalian cell membranes, and involved in the regulation of many cellular processes, including cell survival, angiogenesis, and mitogenesis. The dermal papilla, composed of specialized fibroblasts located in the bulb of the hair follicle, contributes to the control of hair growth and the hair cycle. Objective This study investigated the effect of AA on hair growth by using in vivo and in vitro models. Methods The effect of AA on human dermal papilla cells (hDPCs) and hair shaft elongation was evaluated by MTT assay and hair follicle organ culture, respectively. The expression of various growth and survival factors in hDPCs were investigated by western blot or immunohistochemistry. The ability of AA to induce and prolong anagen phase in C57BL/6 mice was analyzed. Results AA was found to enhance the viability of hDPCs and promote the expression of several factors responsible for hair growth, including fibroblast growth factor-7 (FGF-7) and FGF-10. Western blotting identified the role of AA in the phosphorylation of various transcription factors (ERK, CREB, and AKT) and increased expression of Bcl-2 in hDPCs. In addition, AA significantly promoted hair shaft elongation, with increased proliferation of matrix keratinocytes, during ex vivo hair follicle culture. It was also found to promote hair growth by induction and prolongation of anagen phase in telogen-stage C57BL/6 mice. Conclusion This study concludes that AA plays a role in promoting hair growth by increasing the expression of growth factors in hDPCs and enhancing follicle proliferation and survival. PMID:26848219

CD34 expression in human hair follicles and tricholemmoma: a comprehensive study.

PubMed

Misago, Noriyuki; Toda, Shuji; Narisawa, Yutaka

2011-08-01

There has recently been controversy regarding whether clone My10 is superior to clone QBEND-10 for labeling cells of tricholemmal lineage. Moreover, there have been no previous reports on the CD34 expression in human vellus hair follicles. We performed a comprehensive study of the CD34 expression in human terminal and vellus hair follicles and in 10 tricholemmomas using both the QBEND-10 and the My10 clones. We also performed two different procedures of immunostaining, which included the using of the standard avidin-biotin-peroxidase (ABC) complex system and the Envision system. The most sensitive marker of CD34 for normal human hair follicles and tricholemmomas is QBEND-10 using the ABC system. The degree and strength of the CD34 positive staining mainly depended on the method being used (whether it was the ABC system or the Envision system) rather than the clone. CD34 staining was rarely (20-30%) seen in the anagen and catagen vellus hair follicles, and could only be seen by the QBEND-10 clone using the ABC system. CD34 expression in the tricholemmomas represented either a diffuse or peripheral pattern. CD34 may not be a tricholemmal lineage-specific antigen, but may be related to certain functions of the cells. Copyright © 2011 John Wiley & Sons A/S.

Stem Cell Niche is Partially Lost during Follicular Plucking: A Preliminary Pilot Study

PubMed Central

Kumar, Anil; Gupta, Somesh; Mohanty, Sujata; Bhargava, Balram; Airan, Balram

2013-01-01

Background: Clinical hair transplant studies have revealed that follicular unit extraction (FUE) is superior in terms of stable hair growth in comparison to follicular plucking (FP). Various reasons have been cited for this clinical outcome. FUE and FP are employed to obtain the hair follicle units for hair transplant and recently for cell based therapies in vitiligo. However, there is no scientific data available on the comparison of stem cell fraction in the cell suspension obtained by FUE and FP. Therefore, we undertook this study to compare the percentage of stem cells in the hair follicle obtained by FUE and FP. Objective: The purpose of the following study is to evaluate the quantitative stem cell pool in the hair follicle obtained by FUE and FP. Materials and Methods: A total of 3 human subjects were enrolled with age groups of 17-25 years. Both methods of tissue harvest: FUE and FP; were employed on each subject. There was no vitiligo lesion on the scalp in any of the patients. Hair follicles were incubated with trypsin-EDTA solution at 37°C for 90 min to separate outer root sheath cells. The cell suspension was passed through a 70 μm cell strainer; filtrate was centrifuged to obtain the cell pellet. Cells were labeled with cluster of differentiation (CD200) antibody and acquired with flowcytometry. Results: The mean percentage of CD200 positive cells in FUE and FP method come out to be 8.43 and 1.63 respectively (P = 0.0152). Conclusion: FUE is a better method of the hair follicle harvesting for cell based applications as the stem cell fraction is significantly higher in comparison to FP. PMID:24403776

Follicular and percutaneous penetration pathways of topically applied minoxidil foam.

PubMed

Blume-Peytavi, Ulrike; Massoudy, Lida; Patzelt, Alexa; Lademann, Jürgen; Dietz, Ekkehart; Rasulev, Utkur; Garcia Bartels, Natalie

2010-11-01

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances. This study investigates a selective closure technique of hair follicle orifices in vivo assessing interfollicular and follicular absorption rates of topical minoxidil foam in humans. In delimited skin area, single hair orifices or interfollicular skin were blocked with a microdrop of special varnish-wax-mixture in vivo. Minoxidil foam (5%) was topically applied, and transcutaneous absorption was measured by a new surface ionization mass spectrometry technique in serum. Different settings (open, closed or none of both) enabled to clearly distinguish between interfollicular and follicular penetration of the topically applied minoxidil foam. Five minutes after topical application, minoxidil was detected in blood samples when follicles remained open, whereas with closed follicles 30 min were needed. Highest levels were found first when both pathways were open, followed by open follicles and subsequently by closed follicles. These results demonstrate the high importance of the follicular penetration pathway. Hair follicles are surrounded by a dense network of blood capillaries and dendritic cells and have stem cells in their immediate vicinity, making them ideal targets for drug delivery. Copyright © 2010 Elsevier B.V. All rights reserved.

The role of hair follicles in the percutaneous absorption of caffeine.

PubMed

Otberg, Nina; Patzelt, Alexa; Rasulev, Utkur; Hagemeister, Timo; Linscheid, Michael; Sinkgraven, Ronald; Sterry, Wolfram; Lademann, Jürgen

2008-04-01

* In recent years, it has been suggested that hair follicles represent important shunt routes into the skin for drugs and chemicals [1-3]. * In vitro studies have shown the importance of skin appendages for skin penetration by hydrophilic compounds [4]. Investigation of follicular penetration in vivo has been difficult due to the absence of appropriate analytical methods or suitable animal model systems. * Recently, a new method was described that quantifies follicular penetration in vivo by using selective closure of hair follicles [5]. * Caffeine is frequently used in skin penetration experiments as a model for highly water-soluble compounds. Occlusion [6] and skin thickness [7] seem to have little influence on the penetration of caffeine. However, percutaneous absorption rates for caffeine exhibit regional skin differences in humans in vivo[1]. * The results of the present study demonstrate that a fast drug delivery of caffeine occurs through shunt routes. Therefore, hair follicles are considerable weak spots in our protective sheath against penetration into the body by hydrophilic substances. * We showed that there is a quantitative distinction between follicular penetration and interfollicular diffusion of caffeine in vivo. * These findings are of importance for the development and optimization of topically applied drugs and cosmetics. In addition, such properties must be considered in the development of skin protection measures. The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans. Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish-wax-mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance. Caffeine (3.75 ng ml(-1)) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml(-1)). Highest values (11.75 ng caffeine ml(-1)) were found 1 h after application when the follicles were open. Our findings demonstrate that hair follicles are considerable weak spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances.

Sensory Hairs in the Bowhead Whale, Balaena mysticetus (Cetacea, Mammalia).

PubMed

Drake, Summer E; Crish, Samuel D; George, John C; Stimmelmayr, Raphaella; Thewissen, J G M

2015-07-01

We studied the histology and morphometrics of the hairs of bowhead whales (Balaena mysticetus). These whales are hairless except for two patches of more than 300 hairs on the rostral tip of the lower lip and chin, the rostral tip of the upper lip, and a bilateral row of approximately ten hairs caudal to the blowhole. Histological data indicate that hairs in all three of these areas are vibrissae: they show an outermost connective tissue capsule, a circumferential blood sinus system surrounding the hair shaft, and dense innervation to the follicle. Morphometric data were collected on hair diameters, epidermal recess diameters, hair follicle length, and external hair lengths. The main difference between the hairs in the different regions is that blowhole hairs have larger diameters than the hairs in the chin and rostrum regions. We speculate that the hair shaft thickness patterns in bowheads reflect functional specializations. © 2015 Wiley Periodicals, Inc.

FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells.

PubMed

Nguyen, Minh Binh; Cohen, Idan; Kumar, Vinod; Xu, Zijian; Bar, Carmit; Dauber-Decker, Katherine L; Tsai, Pai-Chi; Marangoni, Pauline; Klein, Ophir D; Hsu, Ya-Chieh; Chen, Ting; Mikkola, Marja L; Ezhkova, Elena

2018-06-13

Merkel cells are innervated mechanosensory cells responsible for light-touch sensations. In murine dorsal skin, Merkel cells are located in touch domes and found in the epidermis around primary hairs. While it has been shown that Merkel cells are skin epithelial cells, the progenitor cell population that gives rise to these cells is unknown. Here, we show that during embryogenesis, SOX9-positive (+) cells inside hair follicles, which were previously known to give rise to hair follicle stem cells (HFSCs) and cells of the hair follicle lineage, can also give rise to Merkel Cells. Interestingly, while SOX9 is critical for HFSC specification, it is dispensable for Merkel cell formation. Conversely, FGFR2 is required for Merkel cell formation but is dispensable for HFSCs. Together, our studies uncover SOX9(+) cells as precursors of Merkel cells and show the requirement for FGFR2-mediated epithelial signalling in Merkel cell specification.

[Human papillomavirus in the pubic hair follicles of men and cervical lesions in their female sexual partners].

PubMed

Han, Tao; Sun, Xuan; Wang, You-Bao; Zhu, Chang-Ming; Xu, Xiang-Qian

2013-09-01

To investigate the association of human papillomavirus (HPV) in the pubic hair follicles of males with HPV infection in their female sexual partners. We included in this study 21 female patients with HPV infection, including 8 cases of cervical cancer, 5 cases of atypical cervical hyperplasia, 5 cases of cervical condyloma, and 3 cases with unidentified causes. We also enlisted 52 men without visible condyloma acuminatum in the external genitalia as healthy controls. We detected HPV in the pubic hair follicles of the female patients' male sexual partners and the healthy male controls by PCR and reverse hybridization in situ. HPV positive was found in 6 (28.6%) of the 21 women's male partners, in whom the HPV types were correspondent situ. to those of the female patients. HPV in the pubic hair follicles of men might be one of the causes of HPV-related cervical lesions in their female sexual partners.

15-deoxy prostaglandin J2, the nonenzymatic metabolite of prostaglandin D2, induces apoptosis in keratinocytes of human hair follicles: a possible explanation for prostaglandin D2-mediated inhibition of hair growth.

PubMed

Joo, Hyun Woo; Kang, Yoo Ri; Kwack, Mi Hee; Sung, Young Kwan

2016-07-01

Recent studies have shown that prostaglandin D2 (PGD2) and its nonenzymatic metabolite, 15-deoxy-Δ(12,14)-prostaglandin J2 (15-dPGJ2), inhibit in vitro growth of explanted human hair follicles and inhibit hair growth in mice through the GPR44 (DP2). However, the underlying mechanism is still unclear. In this study, we first investigated the expression of DP2 in human hair follicles and in cultured follicular cells. We found that DP2 is strongly expressed in the outer root sheath (ORS) cells and weakly expressed in the dermal papilla (DP) cells. We observed slight growth stimulation when ORS and DP cells were treated with PGD2. We also observed slight growth stimulation when DP and ORS cells were treated with low concentrations (0.5 and 1 μM) of 15-dPGJ2. However, 5 μM 15-dPGJ2 inhibited the viability and caused apoptosis of both cell types. Exposure of cultured human hair follicles to 15-dPGJ2 resulted in significant apoptosis in follicular keratinocytes. Altogether, our data provide an evidence that 15-dPGJ2 promotes apoptosis in follicular keratinocytes and provide rationale for developing remedies for the prevention and treatment of hair loss based on DP2 antagonism.

Hair Growth-Promoting Effects of Lavender Oil in C57BL/6 Mice

PubMed Central

Lee, Boo Hyeong; Lee, Jae Soon; Kim, Young Chul

2016-01-01

The purpose of this study was to determine the hair growth effects of lavender oil (LO) in female C57BL/6 mice. The experimental animals were divided into a normal group (N: saline), a vehicle control group (VC: jojoba oil), a positive control group (PC: 3% minoxidil), experimental group 1 (E1: 3% LO), and experimental group 2 (E2: 5% LO). Test compound solutions were topically applied to the backs of the mice (100 μL per application), once per day, 5 times a week, for 4 weeks. The changes in hair follicle number, dermal thickness, and hair follicle depth were observed in skin tissues stained with hematoxylin and eosin, and the number of mast cells was measured in the dermal and hypodermal layers stained with toluidine blue. PC, E1, and E2 groups showed a significantly increased number of hair follicles, deepened hair follicle depth, and thickened dermal layer, along with a significantly decreased number of mast cells compared to the N group. These results indicated that LO has a marked hair growth-promoting effect, as observed morphologically and histologically. There was no significant difference in the weight of the thymus among the groups. However, both absolute and relative weights of the spleen were significantly higher in the PC group than in the N, VC, E1, or E2 group at week 4. Thus, LO could be practically applied as a hair growth-promoting agent. PMID:27123160

Hair Growth-Promoting Effects of Lavender Oil in C57BL/6 Mice.

PubMed

Lee, Boo Hyeong; Lee, Jae Soon; Kim, Young Chul

2016-04-01

The purpose of this study was to determine the hair growth effects of lavender oil (LO) in female C57BL/6 mice. The experimental animals were divided into a normal group (N: saline), a vehicle control group (VC: jojoba oil), a positive control group (PC: 3% minoxidil), experimental group 1 (E1: 3% LO), and experimental group 2 (E2: 5% LO). Test compound solutions were topically applied to the backs of the mice (100 μL per application), once per day, 5 times a week, for 4 weeks. The changes in hair follicle number, dermal thickness, and hair follicle depth were observed in skin tissues stained with hematoxylin and eosin, and the number of mast cells was measured in the dermal and hypodermal layers stained with toluidine blue. PC, E1, and E2 groups showed a significantly increased number of hair follicles, deepened hair follicle depth, and thickened dermal layer, along with a significantly decreased number of mast cells compared to the N group. These results indicated that LO has a marked hair growth-promoting effect, as observed morphologically and histologically. There was no significant difference in the weight of the thymus among the groups. However, both absolute and relative weights of the spleen were significantly higher in the PC group than in the N, VC, E1, or E2 group at week 4. Thus, LO could be practically applied as a hair growth-promoting agent.

A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

PubMed Central

Zhang, Peipei; Kling, Russell E; Ravuri, Sudheer K; Kokai, Lauren E; Rubin, J Peter; Chai, Jia-ke

2014-01-01

Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration. PMID:25383178

Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion

PubMed Central

Tong, Xuemei; Coulombe, Pierre A.

2006-01-01

Mammalian hair follicles cycle between stages of rapid growth (anagen) and metabolic quiescence (telogen) throughout life. Transition from anagen to telogen involves an intermediate stage, catagen, consisting of a swift, apoptosis-driven involution of the lower half of the follicle. How catagen is coordinated, and spares the progenitor cells needed for anagen re-entry, is poorly understood. Keratin 17 (K17)-null mice develop alopecia in the first week post-birth, correlating with hair shaft fragility and untimely apoptosis in the hair bulb. Here we show that this abnormal apoptosis reflects premature entry into catagen. Of the proapoptotic challenges tested, K17-null skin keratinocytes in primary culture are selectively more sensitive to TNFα. K17 interacts with TNF receptor 1 (TNFR1)-associated death domain protein (TRADD), a death adaptor essential for TNFR1-dependent signal relay, suggesting a functional link between this keratin and TNFα signaling. The activity of NF-κB, a downstream target of TNFα, is increased in K17-null skin. We also find that TNFα is required for a timely anagen–catagen transition in mouse pelage follicles, and that its ablation partially rescues the hair cycling defect of K17-null mice. These findings identify K17 and TNFα as two novel and interdependent regulators of hair cycling. PMID:16702408

TGF-beta is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis.

PubMed

Inoue, Keita; Aoi, Noriyuki; Yamauchi, Yuji; Sato, Takahiro; Suga, Hirotaka; Eto, Hitomi; Kato, Harunosuke; Tabata, Yasuhiko; Yoshimura, Kotaro

2009-01-01

Dermal papilla cells (DPCs) in the mammalian hair follicle have been shown to develop hair follicles through epithelial-mesenchymal interactions. A cell therapy to regenerate human hair is theoretically possible by expanding autologous human DPCs (hDPCs) and transplanting them into bald skin, though much remains to be overcome before clinical success. In this study, we compared gene signatures of hDPCs at different passages and human dermal fibroblasts, and found transforming growth factor (TGF)-beta(2) to be highly expressed in cultured hDPCs. Keratinocyte conditioned medium, which is known to help preserve the hair-inducing capacity of hDPCs, up-regulated TGF-beta(2) expression of hDPCs and also enhanced their alkaline phosphatase (ALP) activity, a known index for hair-inductive capacity. Through screening of components secreted from keratinocytes, the vitamin D(3) analogue was found to promote TGF-beta(2) expression and ALP activity of hDPCs. In animal hair folliculogenesis models using rat epidermis and expanded hDPCs, inhibition of TGF-beta(2) signalling at the ligand or receptor level significantly impaired hair folliculogenesis and maturation. These results suggest an important role for TGF-beta(2) in hair follicle morphogenesis and provide insights into the establishment of future cell therapies for hair regrowth by transplanting expanded DPCs.

Hair follicle nevus in a distribution following Blaskho's lines.

PubMed

Germain, Marguerite; Smith, Kathleen J

2002-05-01

We present a case of a rare follicular hamartoma, a hair follicle nevus. Although most previous reports have been solitary lesions, the case we are reporting had multiple papules and nodules following Blaskho's lines. There have been no reports of malignancies arising in these hamartomas.

The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin.

PubMed

Stelnicki, E J; Kömüves, L G; Holmes, D; Clavin, W; Harrison, M R; Adzick, N S; Largman, C

1997-10-01

In order to identify homeobox genes which may regulate skin development and possibly mediate scarless fetal wound healing we have screened amplified human fetal skin cDNAs by polymerase chain reaction (PCR) using degenerate oligonucleotide primers designed against highly conserved regions within the homeobox. We identified three non-HOX homeobox genes, MSX-1, MSX-2, and MOX-1, which were differentially expressed in fetal and adult human skin. MSX-1 and MSX-2 were detected in the epidermis, hair follicles, and fibroblasts of the developing fetal skin by in situ hybridization. In contrast, MSX-1 and MSX-2 expression in adult skin was confined to epithelially derived structures. Immunohistochemical analysis of these two genes suggested that their respective homeoproteins may be differentially regulated. While Msx-1 was detected in the cell nucleus of both fetal and adult skin; Msx-2 was detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in adult epidermis. MOX-1 was expressed in a pattern similar to MSX early in gestation but then was restricted exclusively to follicular cells in the innermost layer of the outer root sheath by 21 weeks of development. Furthermore, MOX-1 expression was completely absent in adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in skin development.

Valproic acid promotes human hair growth in in vitro culture model.

PubMed

Jo, Seong Jin; Choi, Soon-Jin; Yoon, Sun-Young; Lee, Ji Yeon; Park, Won-Seok; Park, Phil-June; Kim, Kyu Han; Eun, Hee Chul; Kwon, Ohsang

2013-10-01

β-Catenin, the transducer of Wnt signaling, is critical for the development and growth of hair follicles. In the absence of Wnt signals, cytoplasmic β-catenin is phosphorylated by glycogen synthase kinase (GSK)-3 and then degraded. Therefore, inhibition of GSK-3 may enhance hair growth via β-catenin stabilization. Valproic acid is an anticonvulsant and a mood-stabilizing drug that has been used for decades. Recently, valproic acid was reported to inhibit GSK-3β in neuronal cells, but its effect on human hair follicles remains unknown. To determine the effect of VPA on human hair growth. We investigated the effect of VPA on cultured human dermal papilla cells and outer root sheath cells and on an in vitro culture of human hair follicles, which were obtained from scalp skin samples of healthy volunteers. Anagen induction by valproic acid was evaluated using C57BL/6 mice model. Valproic acid not only enhanced the viability of human dermal papilla cells and outer root sheath cells but also promoted elongation of the hair shaft and reduced catagen transition of human hair follicles in organ culture model. Valproic acid treatment of human dermal papilla cells led to increased β-catenin levels and nuclear accumulation and inhibition of GSK-3β by phosphorylation. In addition, valproic acid treatment accelerated the induction of anagen hair in 7-week-old female C57BL/6 mice. Valproic acid enhanced human hair growth by increasing β-catenin and therefore may serve as an alternative therapeutic option for alopecia. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

In vivo hair growth-promoting effect of rice bran extract prepared by supercritical carbon dioxide fluid.

PubMed

Choi, Jae-Suk; Jeon, Min-Hee; Moon, Woi-Sook; Moon, Jin-Nam; Cheon, Eun Jin; Kim, Joo-Wan; Jung, Sung Kyu; Ji, Yi-Hwa; Son, Sang Wook; Kim, Mi-Ryung

2014-01-01

The potential hair growth-promoting activity of rice bran supercritical CO2 extract (RB-SCE) and major components of RB-SCE, linoleic acid, policosanol, γ-oryzanol, and γ-tocotrienol, were evaluated with the histological morphology and mRNA expression levels of cell growth factors using real-time reverse transcriptase-polymerase chain reaction (PCR) in C57BL/6 mice. RB-SCE showed hair growth-promoting potential to a similar extent as 3% minoxidil, showing that the hair follicles were induced to be in the anagen stage. The numbers of the hair follicles were significantly increased. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and keratinocyte growth factor (KGF) were also significantly increased and that of transforming growth factor-β (TGF-β) decreased in RB-SCE-treated groups. Among the major components of RB-SCE, linoleic acid and γ-oryzanol induced the formation of hair follicles according to examination of histological morphology and mRNA expression levels of cell growth factors. In conclusion, our results demonstrate that RB-SCE, particularly linoleic acid and γ-oryzanol, promotes hair growth and suggests RB-SCE can be applied as hair loss treatment.

Innovative modified hair follicle harvesting technique with reverse rake scalp elevator for lower occipital donor area in follicular unit extraction hair transplantation

PubMed Central

Gharwade, Chandrakant Rambhau

2016-01-01

Follicular unit extraction (FUE) is one of the widely practiced minimally invasive follicular harvesting techniques employed during hair transplantation. FUE technique has an advantage of utilising lower occipital area and supra-auricular region as a safe donor area described by Unger, in addition to the standard occipital donor area used in strip method (follicular unit transplant). Despite its potential advantages such as rapid recovery, minimal scarring and reduced post-operative pain; its widespread acceptance is limited due to various factors in variable contribution like steeper learning curve and potentially higher follicular transection rates (FTRs). The main practical drawbacks in harvesting FUE from lower occipital donor region that lie inferior to the standard donor area, is its acute angle (10°–15°) of emergent hair from scalp skin, higher variance angle (15°–35°) between hairs below the skin and hair exit angle above the skin and comparatively loose scalp, preventing to provide stable platform for punching. Hair transplant surgeon faces difficulty in aligning and engaging the FUE punch leading to very high hair follicle transection rate, and therefore, it is not a preferred site for harvesting follicles in FUE. Authors description of modified technique using reverse rake scalp elevator helps in negating the acute angle of the hair follicles exit from scalp skin and reducing the variance angle between emergent hair and hair below the skin in lower occipital region thereby reducing FTR. Furthermore, an added advantage of reducing the overall operative time and surgeon fatigue, improve donor area healing, availability of a comparatively larger donor area which increases the confidence of the beginners. This method will be of help as it is easy to duplicate and follow by novice hair transplant surgeons and also for those who are routinely doing mega hair transplants sessions. PMID:28216821

The Female Pattern Hair Loss: Review of Etiopathogenesis and Diagnosis

PubMed Central

Vujovic, Anja; Del Marmol, Véronique

2014-01-01

Female pattern hair loss (FPHL) is the most common hair loss disorder in women. Initial signs may develop during teenage years leading to a progressive hair loss with a characteristic pattern distribution. The condition is characterized by progressive replacement of terminal hair follicles over the frontal and vertex regions by miniaturized follicles, that leads progressively to a visible reduction in hair density. Women diagnosed with FPHL may undergo significant impairment of quality of life. FPHL diagnosis is mostly clinical. Depending on patient history and clinical evaluation, further diagnostic testing may be useful. The purpose of the paper is to review the current knowledge about epidemiology, pathogenesis, clinical manifestations, and diagnosis of FPHL. PMID:24812631

Enhancing hair follicle regeneration by nonablative fractional laser: Assessment of irradiation parameters and tissue response.

PubMed

Wu, Yueh-Feng; Wang, Shiou-Han; Wu, Pei-Shan; Fan, Sabrina Mai-Yi; Chiu, Hsien-Yi; Tsai, Tsung-Hua; Lin, Sung-Jan

2015-04-01

Identification of methods to enhance anagen entry can be helpful for alopecia. Recently, nonablative laser has been proposed as a potential treatment for alopecia. However, how the laser parameters affect stem cell activity, hair cycles and the associated side effects have not been well characterized. Here we examine the effects of irradiation parameters of 1,550-nm fractional laser on hair cycles. The dorsal skin of eight-week-old female C57BL/6 mice with hair follicles in synchronized telogen was shaved and irradiated with a 1,550-nm fractional erbium-glass laser (Fraxel RE:STORE (SR1500) Laser System, Solta Medical, U.S.A.) with varied beam energies (5-35 mJ) and beam densities (500-3500 microthermal zones/cm(2) ). The cutaneous changes were evaluated both grossly and histologically. Hair follicle stem cell activity was detected by BrdU incorporation and changes in gene expression were quantified by real-time PCR. Direct thermal injury to hair follicles could be observed early after irradiation, especially at higher beam energy. Anagen induction in the irradiated skin showed an all-or-non change. Anagen induction and ulcer formation were affected by the combination of beam energy and density. The lowest beam energy of 5 mJ failed to promote anagen entry at all beam densities tested. As beam energy increased from 10 mJ to 35 mJ, we found a decreasing trend of beam density that could induce anagen entry within 7-9 days with activation of hair follicle stem cells. Beam density above the pro-regeneration density could lead to ulcers and scarring followed by anagen entry in adjacent skin. Analysis of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, revealed that transient moderate inflammation was associated with anagen induction and intense prolonged inflammation preceded ulcer formation. To avoid side effects of hair follicle injury and scarring, appropriate combination of beam energy and density is required. Parameters outside the therapeutic window can result in either no anagen promotion or ulcer formation. © 2015 Wiley Periodicals, Inc.

Self-Organizing and Stochastic Behaviors During the Regeneration of Hair Stem Cells

PubMed Central

Plikus, Maksim V.; Baker, Ruth E.; Chen, Chih-Chiang; Fare, Clyde; de la Cruz, Damon; Andl, Thomas; Maini, Philip K.; Millar, Sarah E.; Widelitz, Randall; Chuong, Cheng-Ming

2012-01-01

Stem cells cycle through active and quiescent states. Large populations of stem cells in an organ may cycle randomly or in a coordinated manner. Although stem cell cycling within single hair follicles has been studied, less is known about regenerative behavior in a hair follicle population. By combining predictive mathematical modeling with in vivo studies in mice and rabbits, we show that a follicle progresses through cycling stages by continuous integration of inputs from intrinsic follicular and extrinsic environmental signals based on universal patterning principles. Signaling from the WNT/bone morphogenetic protein activator/inhibitor pair is coopted to mediate interactions among follicles in the population. This regenerative strategy is robust and versatile because relative activator/inhibitor strengths can be modulated easily, adapting the organism to different physiological and evolutionary needs. PMID:21527712

Topical Modulation of the Burn Wound Inflammatory Response to Improve Short and Long Term Outcomes

DTIC Science & Technology

2016-10-01

Duroc pig. We hypothesize that topical p38MAPK inhibition will attenuate the depth of the burn by preventing hair -follicle cell apoptosis, attenuate...Intracellular MAPK Hair -Follicle Apoptosis Local/Dermal Inflammatory Cell Activation SIRS End-Organ Failure Topical MAPK Inhibitors Production of

Human hair follicles contain two forms of ATP-sensitive potassium channels, only one of which is sensitive to minoxidil.

PubMed

Shorter, Katie; Farjo, Nilofer P; Picksley, Steven M; Randall, Valerie A

2008-06-01

Hair disorders cause psychological distress but are generally poorly controlled; more effective treatments are required. Despite the long-standing use of minoxidil for balding, its mechanism is unclear; suggestions include action on vasculature or follicle cells. Similar drugs also stimulate hair, implicating ATP-sensitive potassium (K(ATP)) channels. To investigate whether K(ATP) channels are present in human follicles, we used organ culture, molecular biological, and immunohistological approaches. Minoxidil and tolbutamide, a K(ATP) channel blocker, opposed each other's effects on the growing phase (anagen) of scalp follicles cultured in media with and without insulin. Reverse transcriptase-polymerase chain reaction identified K(ATP) channel component gene expression including regulatory sulfonylurea receptors (SUR) SUR1 and SUR2B but not SUR2A and pore-forming subunits (Kir) Kir6.1 and Kir6.2. When hair bulb tissues were examined separately, epithelial matrix expressed SUR1 and Kir6.2, whereas both dermal papilla and sheath exhibited SUR2B and Kir6.1. Immunohistochemistry demonstrated similar protein distributions. Thus, human follicles respond biologically to K(ATP) channel regulators in culture and express genes and proteins for two K(ATP) channels, Kir6.2/SUR1 and Kir6.1/SUR2B; minoxidil only stimulates SUR2 channels. These findings indicate that human follicular dermal papillae contain K(ATP) channels that can respond to minoxidil and that tolbutamide may suppress hair growth clinically; novel drugs designed specifically for these channels could treat hair disorders.

Fullerene nanomaterials potentiate hair growth.

PubMed

Zhou, Zhiguo; Lenk, Robert; Dellinger, Anthony; MacFarland, Darren; Kumar, Krishan; Wilson, Stephen R; Kepley, Christopher L

2009-06-01

Hair loss is a common symptom resulting from a wide range of disease processes and can lead to stress in affected individuals. The purpose of this study was to examine the effect of fullerene nanomaterials on hair growth. We used shaved mice as well as SKH-1 "bald" mice to determine if fullerene-based compounds could affect hair growth and hair follicle numbers. In shaved mice, fullerenes increase the rate of hair growth as compared with mice receiving vehicle only. In SKH-1 hairless mice fullerene derivatives given topically or subdermally markedly increased hair growth. This was paralleled by a significant increase in the number of hair follicles in fullerene-treated mice as compared with those mice treated with vehicle only. The fullerenes also increased hair growth in human skin sections maintained in culture. These studies have wide-ranging implications for those conditions leading to hair loss, including alopecia, chemotherapy, and reactions to various chemicals.

A hypothetical pathogenesis model for androgenic alopecia: clarifying the dihydrotestosterone paradox and rate-limiting recovery factors.

PubMed

English, Robert S

2018-02-01

Androgenic alopecia, also known as pattern hair loss, is a chronic progressive condition that affects 80% of men and 50% of women throughout a lifetime. But despite its prevalence and extensive study, a coherent pathology model describing androgenic alopecia's precursors, biological step-processes, and physiological responses does not yet exist. While consensus is that androgenic alopecia is genetic and androgen-mediated by dihydrotestosterone, questions remain regarding dihydrotestosterone's exact role in androgenic alopecia onset. What causes dihydrotestosterone to increase in androgenic alopecia-prone tissues? By which mechanisms does dihydrotestosterone miniaturize androgenic alopecia-prone hair follicles? Why is dihydrotestosterone also associated with hair growth in secondary body and facial hair? Why does castration (which decreases androgen production by 95%) stop pattern hair loss, but not fully reverse it? Is there a relationship between dihydrotestosterone and tissue remodeling observed alongside androgenic alopecia onset? We review evidence supporting and challenging dihydrotestosterone's causal relationship with androgenic alopecia, then propose an evidence-based pathogenesis model that attempts to answer the above questions, account for additionally-suspected androgenic alopecia mediators, identify rate-limiting recovery factors, and elucidate better treatment targets. The hypothesis argues that: (1) chronic scalp tension transmitted from the galea aponeurotica induces an inflammatory response in androgenic alopecia-prone tissues; (2) dihydrotestosterone increases in androgenic alopecia-prone tissues as part of this inflammatory response; and (3) dihydrotestosterone does not directly miniaturize hair follicles. Rather, dihydrotestosterone is a co-mediator of tissue dermal sheath thickening, perifollicular fibrosis, and calcification - three chronic, progressive conditions concomitant with androgenic alopecia progression. These conditions remodel androgenic alopecia-prone tissues - restricting follicle growth space, oxygen, and nutrient supply - leading to the slow, persistent hair follicle miniaturization characterized in androgenic alopecia. If true, this hypothetical model explains the mechanisms by which dihydrotestosterone miniaturizes androgenic alopecia-prone hair follicles, describes a rationale for androgenic alopecia progression and patterning, makes sense of dihydrotestosterone's paradoxical role in hair loss and hair growth, and identifies targets to further improve androgenic alopecia recovery rates: fibrosis, calcification, and chronic scalp tension. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

[Tufted hair folliculitis].

PubMed

Trüeb, R M; Pericin, M; Hafner, J; Burg, G

1997-04-01

A case of tufted hair folliculutis presenting as circumscribed, tender and inflamed areas in the occiput with residual tufted follicles in a 28-year old man is reported. Tufted hair folliculitis is a characteristic localized scarring bacterial folliculitis of the scalp due to Staphylococcus aureus. Histopathological studies reveal perifollicular inflammation around the upper portions of the follicles sparing the hair root level. Within areas of inflammation, several follicles converge toward a common follicular duct with a widely dilated opening. Currently, tufted hair folliculitis is considered a variant of folliculitis decalvans of Quinquaud. Staphylococcal infection is believed to be an initial causative factor, and underlying differences in follicular anatomy or host response may be important in determining which reaction pattern occurs in an affected individual. The development of atrophy with loss of adnexal structures (in folliculitis decalvans) or of hair tufts (in tufting folliculitis) may depend upon the depth and destructive potential of the inflammatory process. The therapeutic approach is problematic; prolonged treatment with oral antibiotics may stabilize the disease, but good and at times more definitive results (as in the presented case) have been reported after radical surgical excision of the involved areas.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouji, Yukiteru; Yoshikawa, Masahide; Moriya, Kei

Wnts are deeply involved in the proliferation and differentiation of skin epithelial cells. We previously reported the differentiation of cultured primary skin epithelial cells toward hair shaft and inner root sheath (IRS) of the hair follicle via {beta}-catenin stabilization caused by Wnt-10b, however, the effects of Wnt-10b on cultured hair follicles have not been reported. In the present study, we examined the effects of Wnt-10b on shaft growth using organ cultures of whisker hair follicles in serum-free conditions. No hair shaft growth was observed in the absence of Wnt-10b, whereas its addition to the culture promoted elongation of the hairmore » shaft, intensive incorporation of BrdU in matrix cells flanking the dermal papilla (DP), and {beta}-catenin stabilization in DP and IRS cells. These results suggest a promoting effect of Wnt-10b on hair shaft growth that is involved with stimulation of the DP via Wnt-10b/{beta}-catenin signalling, proliferation of matrix cells next to the DP, and differentiation of IRS cells by Wnt-10b.« less

The preventive effect of vitamin D3 on radiation-induced hair toxicity in a rat model.

PubMed

Baltalarli, Bahar; Bir, Ferda; Demirkan, Neşe; Abban, Gülçin

2006-02-28

Our aim is to investigate the protective effect of vitamin D3 especially from radiation-induced hair toxicity. A model of skin radiation injury was developed and a single fraction of 20 Gy Gamma irradiation was applied to the right dorsal skin of fourteen rats. All animals were randomly divided into 2 groups: Group I: irradiation alone (n = 7) and Group II: irradiation and 0.2 microg vitamin D3 given IM (n = 7). Fifty days after post-irradiation rats were sacrificed. The outcomes were evaluated on the basis of histopathological findings and immunohistochemical staining for Vitamin D receptor (VDR) in skin and hair follicles. The number of hair follicles in the radiation field for the group of animals irradiated without pretreatment was significantly lower than outside of the irradiated area (p = 0.016) as it is expected. Contrarily the number of hair follicles did not show significant difference in the pretreated group between the irradiated field and outside of the fields (p = 0,14). Skin of the vitamin D3 pretreated group demonstrated stronger immunoreactivity for VDR compared to irradiation alone group. These results indicate that administration of vitamin D3 may protect hair follicles from radiation toxicity. Further clinical trials should be conducted to prove the preventive effect of vitamin D3 as well as dosing and timing of the agent on radiation-induced alopecia.

Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata).

PubMed

Siebenhaar, Frank; Sharov, Andrey A; Peters, Eva M J; Sharova, Tatyana Y; Syska, Wolfgang; Mardaryev, Andrei N; Freyschmidt-Paul, Pia; Sundberg, John P; Maurer, Marcus; Botchkarev, Vladimir A

2007-06-01

Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its expression and effects on immune cells in a C3H/HeJ mouse model for AA. During early stages of AA development, the number of SP-immunoreactive nerve fibers in skin is increased, compared to non-affected mice. However, during advanced stages of AA, the number of SP-immunoreactive nerves and SP protein levels in skin are decreased, whereas the expression of the SP-degrading enzyme neutral endopeptidase (NEP) is increased, compared to control skin. In AA, NK-1R is expressed on CD8+ lymphocytes and macrophages accumulating around affected hair follicles. Additional SP supply to the skin of AA-affected mice leads to a significant increase of mast cell degranulation and to accelerated hair follicle regression (catagen), accompanied by an increase of CD8+ cells-expressing granzyme B. These data suggest that SP, NEP, and NK-1R serve as important regulators in the molecular signaling network modulating inflammatory response in autoimmune hair loss.

Molecular genetics of the hair follicle: the state of the art.

PubMed

Van Steensel, M A; Happle, R; Steijlen, P M

2000-01-01

For those who are interested in the biology of skin and its derivatives, these are interesting times indeed. In a mere 5 years, the field has been revolutionized by the application of molecular genetics to human congenital skin disorders. Where dermatology first was limited to observation and empirics, there are now DNA-diagnostics, rational drug design, and perhaps even gene therapy available soon. In particular, the study of rare human syndromes involving abnormalities of hair growth and structure has yielded new insights into the regulation of cell growth and differentiation in the hair follicle. As this structure shows a cyclic pattern of differentiation, it may give new information concerning the regulation of cell differentiation in general. This review covers the recent developments in this fast-moving field. First, we will give a short introduction to (structural) hair biology. Next, we will try to fit these data into the framework of what is already known and attempt to present a unified model for hair follicle growth and differentiation.

1α,25-Dihydroxyvitamin D3 Modulates the Hair-Inductive Capacity of Dermal Papilla Cells: Therapeutic Potential for Hair Regeneration

PubMed Central

Aoi, Noriyuki; Inoue, Keita; Chikanishi, Toshihiro; Fujiki, Ryoji; Yamamoto, Hanako; Kato, Harunosuke; Eto, Hitomi; Doi, Kentaro; Itami, Satoshi; Kato, Shigeaki

2012-01-01

Dermal papilla cells (DPCs) have the potential to induce differentiation of epithelial stem cells into hair, and Wnt signaling is deeply involved in the initiation process. The functional limitation of expanded adult DPCs has been a difficult challenge for cell-based hair regrowth therapy. We previously reported that 1α,25-dihydroxyvitamin D3 (VD3) upregulates expression of transforming growth factor (TGF)-β2 and alkaline phosphatase (ALP) activity, both features of hair-inducing human DPCs (hDPCs). In this study, we further examined the effects and signaling pathways associated with VD3 actions on DPCs. VD3 suppressed hDPC proliferation in a dose-dependent, noncytotoxic manner. Among the Wnt-related genes investigated, Wnt10b expression was significantly upregulated by VD3 in hDPCs. Wnt10b upregulation, as well as upregulation of ALPL (ALP, liver/bone/kidney) and TGF-β2, by VD3 was specific in hDPCs and not detected in human dermal fibroblasts. Screening of paracrine or endocrine factors in the skin indicated that all-trans retinoic acid (atRA) upregulated Wnt10b gene expression, although synergistic upregulation (combined atRA and VD3) was not seen. RNA interference with vitamin D receptor (VDR) revealed that VD3 upregulation of Wnt10b, ALPL, and TGF-β2 was mediated through the genomic VDR pathway. In a rat model of de novo hair regeneration by murine DPC transplantation, pretreatment with VD3 significantly enhanced hair folliculogenesis. Specifically, a greater number of outgrowing hair shafts and higher maturation of regenerated follicles were observed. Together, these data suggest that VD3 may promote functional differentiation of DPCs and be useful in preserving the hair follicle-inductive capacity of cultured DPCs for hair regeneration therapies. PMID:23197867

Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline

PubMed Central

Chi, Woo; Wu, Eleanor; Morgan, Bruce A.

2013-01-01

Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss. PMID:23487317

Chitosan nanoparticles for targeting and sustaining minoxidil sulphate delivery to hair follicles.

PubMed

Matos, Breno Noronha; Reis, Thaiene Avila; Gratieri, Taís; Gelfuso, Guilherme Martins

2015-04-01

This work developed minoxidil sulphate-loaded chitosan nanoparticles (MXS-NP) for targeted delivery to hair follicles, which could sustain drug release and improve the topical treatment of alopecia. Chitosan nanoparticles were obtained using low-molecular weight chitosan and tripolyphosphate as crosslink agent. MXS-NP presented a monomodal distribution with hydrodynamic diameter of 235.5 ± 99.9 nm (PDI of 0.31 ± 0.01) and positive zeta potential (+38.6 ± 6.0 mV). SEM analysis confirmed nanoparticles average size and spherical shape. A drug loading efficiency of 73.0 ± 0.3% was obtained with polymer:drug ratio of 1:1 (w/w). Drug release through cellulose acetate membranes from MXS-NP was sustained in about 5 times in comparison to the diffusion rate of MXS from the solution (188.9 ± 6.0 μg/cm(2)/h and 35.4 ± 1.8 μg/cm(2)/h). Drug permeation studies through the skin in vitro, followed by selective recovery of MXS from the hair follicles, showed that MXS-NP application resulted in a two-fold MXS increase into hair follicles after 6h in comparison to the control solution (5.9 ± 0.6 μg/cm(2) and 2.9 ± 0.8 μg/cm(2)). MXS-loading in nanoparticles appears as a promising and easy strategy to target and sustain drug delivery to hair follicles, which may improve the topical treatment of alopecia. Copyright © 2015 Elsevier B.V. All rights reserved.

A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development.

PubMed

Xiao, Ying; Thoresen, Daniel T; Miao, Lingling; Williams, Jonathan S; Wang, Chaochen; Atit, Radhika P; Wong, Sunny Y; Brownell, Isaac

2016-07-01

The Sonic hedgehog (Shh) signaling pathway regulates developmental, homeostatic, and repair processes throughout the body. In the skin, touch domes develop in tandem with primary hair follicles and contain sensory Merkel cells. The developmental signaling requirements for touch dome specification are largely unknown. We found dermal Wnt signaling and subsequent epidermal Eda/Edar signaling promoted Merkel cell morphogenesis by inducing Shh expression in early follicles. Lineage-specific gene deletions revealed intraepithelial Shh signaling was necessary for Merkel cell specification. Additionally, a Shh signaling agonist was sufficient to rescue Merkel cell differentiation in Edar-deficient skin. Moreover, Merkel cells formed in Fgf20 mutant skin where primary hair formation was defective but Shh production was preserved. Although developmentally associated with hair follicles, fate mapping demonstrated Merkel cells primarily originated outside the hair follicle lineage. These findings suggest that touch dome development requires Wnt-dependent mesenchymal signals to establish reciprocal signaling within the developing ectoderm, including Eda signaling to primary hair placodes and ultimately Shh signaling from primary follicles to extrafollicular Merkel cell progenitors. Shh signaling often demonstrates pleiotropic effects within a structure over time. In postnatal skin, Shh is known to regulate the self-renewal, but not the differentiation, of touch dome stem cells. Our findings relate the varied effects of Shh in the touch dome to the ligand source, with locally produced Shh acting as a morphogen essential for lineage specification during development and neural Shh regulating postnatal touch dome stem cell maintenance.

Tamoxifen-loaded liposomal topical formulation arrests hair growth in mice.

PubMed

Bhatia, A; Singh, B; Amarji, B; Katare, O P

2010-08-01

For several decades, androgens have dominated endocrine research in the domain of hair growth control. However, it has long been known that oestrogens also tend to alter hair follicle (HF) growth and cycling significantly by binding to locally expressed high-affinity oestrogen receptors (ORs). Tamoxifen (TAM) is a selective OR modulator. The current work aims to investigate the effect of topically applied TAM on the hair growth of mice. Test formulations were applied once daily on the shaved back area of the mice for a period of 5 weeks. The effect of these formulations was studied by visual and histological examinations. Animals treated with saline and placebo gel formulation showed significant hair growth on the 20th day. The number and length of follicles were also found to be normal. In contrast, no hair growth was observed in the animals treated with TAM gel, even after the termination of treatment. The HFs were found to be arrested in telogen phase with clear signs of follicle dystrophy. The hair growth-retarding effect of TAM observed in the current study clearly demonstrates its OR agonistic effect on hair growth. This work also provides a distinct lead towards the possible potential of TAM liposomal gel in the treatment of hirsutism.

The metabolism of testosterone by dermal papilla cells cultured from human pubic and axillary hair follicles concurs with hair growth in 5 alpha-reductase deficiency.

PubMed

Hamada, K; Thornton, M J; Laing, I; Messenger, A G; Randall, V A

1996-05-01

Androgens regulate the growth of many human hair follicles, but only pubic, axillary, and scalp hair growth occur in men with 5 alpha-reductase deficiency. This suggests that 5 alpha-dihydrotestosterone is the active intracellular androgen in androgen-dependent follicles, except in the axilla and pubis. Since the dermal papilla plays a major regulatory role in hair follicles and may be the site of androgen action, we have investigated androgen metabolism in six primary lines of cultured dermal papilla cells from pubic and axillary hair follicles; previous studies have shown that beard cells take up and metabolize testosterone, retaining and secreting 5 alpha-dihydrotestosterone. After 24 h preincubation in serum-free Eagle's medium 199, 100-mm dishes of confluent cells were incubated for 2 h with 5 nM [1,2,6,7-3H]testosterone. Media were collected and the cells washed with phosphate-buffered saline and extracted with chloroform: methanol (2:1). After the addition of unlabeled and 14C-labeled marker steroids, the extracts were analyzed by a two-step thin-layer chromatography system; steroid identity was confirmed by recrystallization to a constant 3H/14C ratio. Beard and pubic dermal papilla cells were also incubated for 24 h, and the medium was analyzed at various times. The results from pubic and axillary primary cell lines were similar. In both cells and media the major steroid identified was testosterone, but significant amounts of androstenedione were present, indicating 17 beta-hydroxysteroid dehydrogenase activity; androstenedione was also identified within the cells, but a small amount of 5 alpha-dihydrotestosterone was only identified in one pubic cell line. Beard dermal papilla cells secreted large amounts of 5 alpha-dihydrotestosterone into the medium over 24 h in contrast to pubic cells, which produced only very small amounts. The pubic and axillary cell results contrasts with the observations of pronounced 5 alpha-dihydrotestosterone in beard cells and confirm that androgen metabolism in cultured dermal papilla cells reflects the parent follicle's ability to respond to androgen in the absence of 5 alpha-reductase type II in vivo. This supports our hypothesis that androgen acts on hair follicles via the dermal papilla and suggests that cultured dermal papilla cells may offer an important model system for studies of androgen action.

Follicular penetration of topically applied caffeine via a shampoo formulation.

PubMed

Otberg, N; Teichmann, A; Rasuljev, U; Sinkgraven, R; Sterry, W; Lademann, J

2007-01-01

Follicular drug delivery is the prerequisite for an effective treatment of androgenetic alopecia or other reasons of premature hair loss. The follicular penetration of caffeine, applied topically in a shampoo formulation for 2 min, was measured with highly sensitive surface ionization in combination with mass spectroscopy, a selective method for the detection of very small quantities of transcutaneously absorbed substances in the blood. An experimental protocol, developed to selectively block the follicular pathway within the test area, was used. Based on this principle, a clear distinction between interfollicular and follicular penetration of topically applied caffeine was feasible. After 2 min, caffeine penetrated via the hair follicles and stratum corneum. It was found that the penetration via hair follicles was faster and higher compared with the interfollicular route and that hair follicles are the only pathway for fast caffeine absorption during the first 20 min after application. Copyright 2007 S. Karger AG, Basel.

Activation of Wnt/β-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in in vitro culture model.

PubMed

Han, Le; Liu, Ben; Chen, Xianyan; Chen, Haiyan; Deng, Wenjia; Yang, Changsheng; Ji, Bin; Wan, Miaojian

2018-04-01

Activation of the Wnt/β-catenin signaling pathway plays an important role in hair follicle morphogenesis and hair growth. Recently, low-level laser therapy (LLLT) was evaluated for stimulating hair growth in numerous clinical studies, in which 655-nm red light was found to be most effective and practical for stimulating hair growth. We evaluated whether 655-nm red light + light-emitting diode (LED) could promote human hair growth by activating Wnt/β-catenin signaling. An in vitro culture of human hair follicles (HFs) was irradiated with different intensities of 655-nm red light + LED, 21 h7 (an inhibitor of β-catenin), or both. Immunofluorescence staining was performed to assess the expression of β-catenin, GSK3β, p-GSK3β, and Lef1 in the Wnt/β-catenin signaling. The 655-nm red light + LED not only enhanced hair shaft elongation, but also reduced catagen transition in human hair follicle organ culture, with the greatest effectiveness observed at 5 min (0.839 J/cm 2 ). Additionally, 655-nm red light + LED enhanced the expression of β-catenin, p-GSK3β, and Lef1, signaling molecules of the Wnt/β-catenin pathway, in the hair matrix. Activation of Wnt/β-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in vitro and therefore may serve as an alternative therapeutic option for alopecia.

Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development

PubMed Central

Bar, Carmit; Tsai, Pai-Chi; Valdes, Victor J.; Cohen, Idan; Santoriello, Francis J.; Zhao, Dejian; Hsu, Ya-Chieh; Ezhkova, Elena

2016-01-01

An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh) signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2) in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures. PMID:27414999

Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development.

PubMed

Perdigoto, Carolina N; Dauber, Katherine L; Bar, Carmit; Tsai, Pai-Chi; Valdes, Victor J; Cohen, Idan; Santoriello, Francis J; Zhao, Dejian; Zheng, Deyou; Hsu, Ya-Chieh; Ezhkova, Elena

2016-07-01

An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh) signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2) in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures.

Identification of hair shaft progenitors that create a niche for hair pigmentation

PubMed Central

Liao, Chung-Ping; Booker, Reid C.; Morrison, Sean J.; Le, Lu Q.

2017-01-01

Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20+ cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes. PMID:28465357

Identification of hair shaft progenitors that create a niche for hair pigmentation.

PubMed

Liao, Chung-Ping; Booker, Reid C; Morrison, Sean J; Le, Lu Q

2017-04-15

Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20 + cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes. © 2017 Liao et al.; Published by Cold Spring Harbor Laboratory Press.

Post-transcriptional Regulation of Keratinocyte Progenitor Cell Expansion, Differentiation and Hair Follicle Regression by miR-22

PubMed Central

Meng, Qingyong; Zhao, Yiqiang; Chen, Lei; Zhang, Hongquan; Xue, Lixiang; Zhang, Xiuqing; Lengner, Christopher; Yu, Zhengquan

2015-01-01

Hair follicles (HF) undergo precisely regulated recurrent cycles of growth, cessation, and rest. The transitions from anagen (growth), to catagen (regression), to telogen (rest) involve a physiological involution of the HF. This process is likely coordinated by a variety of mechanisms including apoptosis and loss of growth factor signaling. However, the precise molecular mechanisms underlying follicle involution after hair keratinocyte differentiation and hair shaft assembly remain poorly understood. Here we demonstrate that a highly conserved microRNA, miR-22 is markedly upregulated during catagen and peaks in telogen. Using gain- and loss-of-function approaches in vivo, we find that miR-22 overexpression leads to hair loss by promoting anagen-to-catagen transition of the HF, and that deletion of miR-22 delays entry to catagen and accelerates the transition from telogen to anagen. Ectopic activation of miR-22 results in hair loss due to the repression a hair keratinocyte differentiation program and keratinocyte progenitor expansion, as well as promotion of apoptosis. At the molecular level, we demonstrate that miR-22 directly represses numerous transcription factors upstream of phenotypic keratin genes, including Dlx3, Foxn1, and Hoxc13. We conclude that miR-22 is a critical post-transcriptional regulator of the hair cycle and may represent a novel target for therapeutic modulation of hair growth. PMID:26020521

mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

PubMed

Deng, Zhili; Lei, Xiaohua; Zhang, Xudong; Zhang, Huishan; Liu, Shuang; Chen, Qi; Hu, Huimin; Wang, Xinyue; Ning, Lina; Cao, Yujing; Zhao, Tongbiao; Zhou, Jiaxi; Chen, Ting; Duan, Enkui

2015-02-01

Hair follicles (HFs) undergo cycles of degeneration (catagen), rest (telogen), and regeneration (anagen) phases. Anagen begins when the hair follicle stem cells (HFSCs) obtain sufficient activation cues to overcome suppressive signals, mainly the BMP pathway, from their niche cells. Here, we unveil that mTOR complex 1 (mTORC1) signaling is activated in HFSCs, which coincides with the HFSC activation at the telogen-to-anagen transition. By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation, we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen. Unexpectedly, BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs. Through both gain- and loss-of-function studies in vitro, we show that mTORC1 signaling negatively affects BMP signaling, which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation. Indeed, in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin. Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Efficacy of low-level laser therapy on hair regrowth in dogs with noninflammatory alopecia: a pilot study.

PubMed

Olivieri, Lara; Cavina, Damiano; Radicchi, Giada; Miragliotta, Vincenzo; Abramo, Francesca

2015-02-01

Canine noninflammatory alopecia (CNA) is a heterogeneous group of skin diseases with different underlying pathogenesis. The therapeutic approach is challenging, and new options for treatment are desirable. To test the clinical efficacy of low-level laser therapy (LLLT) on hair regrowth in CNA. Seven dogs of different ages, breeds and genders with a clinical and histopathological diagnosis of noninflammatory alopecia. Each dog was treated twice weekly for a maximum of 2 months with a therapeutic laser producing the following three different wavelengths emerging simultaneously from 21 foci: 13 × 16 mW, 470 nm; 4 × 50 mW, 685 nm; and 4 × 200 mW, 830 nm. The fluence given was 3 J/cm(2) , frequency 5 Hz, amplitude of the irradiated area was 25 cm(2) and application time was 1.34 min. A predetermined alopecic area was left untreated and served as a control area. From one dog, post-treatment biopsies of treated and untreated sites were obtained for histological evaluation of hair density and the percentage of haired and nonhaired follicles. At the end of the study, coat regrowth was greatly improved in six of seven animals and improved in one of seven. By morphometry, the area occupied by hair follicles was 18% in the treated sample and 11% in the untreated one (11%); haired follicles were (per area) 93% in the treated sample and only 9% in the control sample. Our clinical and histological data document promising effects of LLLT on hair regrowth in CNA. Further studies investigating the biological mechanism underlying the effect of LLLT on hair follicle cycling are warranted. © 2014 ESVD and ACVD.

A novel rat model for chemotherapy-induced alopecia.

PubMed

Wikramanayake, T C; Amini, S; Simon, J; Mauro, L M; Elgart, G; Schachner, L A; Jimenez, J J

2012-04-01

More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. To develop a clinically relevant adult rat model for CIA. We first tested whether neonatal pigmented Long-Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle, and starting 15 days later, the rats were treated with etoposide for 3 days. Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation. A novel, pigmented adult rat model has been established for CIA. By hair-shaft clipping during early telogen, synchronized anagen entry was induced, which resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA, and will be a useful tool to test agents for the prevention and treatment of CIA. © The Author(s). CED © 2012 British Association of Dermatologists.

Frontal fibrosing alopecia in postmenopausal women.

PubMed

Tosti, Antonella; Piraccini, Bianca Maria; Iorizzo, Matilde; Misciali, Cosimo

2005-01-01

Frontal fibrosing alopecia is a variety of cicatricial alopecia characterized by a band of frontal/frontoparietal hair recession and marked decrease or a complete loss of the eyebrows, typically observed in women who are postmenopausal. The purpose of this study was to report clinical and histopathologic findings and results of treatment in a group of women affected by the disease. A total of 14 women with alopecia of the frontal hairline were evaluated from June 2000 through July 2003 in our outpatient consultation for hair disorders. Clinical examination revealed a band of symmetric recession of the frontoparietal hairline extending to the preauricular areas associated with loss of follicular orifices, mild skin atrophy, and perifollicular erythema at the scalp margin. In all, 9 patients also had partial or total loss of the eyebrows. The histologic features of the scalp specimens were similar in all our patients with a reduction of the number of hair follicles, and a high number of intermediate and velluslike follicles. Intemediate and velluslike follicles were more commonly affected than terminal follicles by the lymphocytic inflammatory infiltrate and perifollicular fibrosis. Frontal fibrosing alopecia is a cicatricial alopecia that follows destruction of hair follicles by an inflammatory lymphocytic infiltrate that is localized around the upper portion of the hair follicle. It differs from lichen planopilaris because the lymphocytic infiltrate and fibrosis affect selectively the intermediate and the velluslike follicles of the frontal margin and eyebrows. The reason for this selective involvement is still unknown. Frontal fibrosing alopecia may represent a variety of lichen planopilaris with selective involvement of certain androgen-dependent areas. The affected follicles may have typical biologic markers that could explain the clinical and histologic features found in the disease. It is interesting to note that some of the patients treated with finasteride (2.5 mg/d) showed an arrest in the progression of the disease. Even if there is no proof for a hormonal basis of the disease, the effectiveness of finasteride in some patients may indicate that androgens might be partially responsible of the pathogenesis of the disease.

A PAIR OF TRANSMEMBRANE RECEPTORS ESSENTIAL FOR THE RETENTION AND PIGMENTATION OF HAIR

PubMed Central

Han, Rong; Beppu, Hideyuki; Lee, Yun-Kyoung; Georgopoulos, Katia; Larue, Lionel; Li, En; Weiner, Lorin; Brissette, Janice L.

2012-01-01

Hair follicles are simple, accessible models for many developmental processes. Here, using mutant mice, we show that Bmpr2, a known receptor for bone morphogenetic proteins (Bmps), and Acvr2a, a known receptor for Bmps and activins, are individually redundant but together essential for multiple follicular traits. When Bmpr2/Acvr2a function is reduced in cutaneous epithelium, hair follicles undergo rapid cycles of hair generation and loss. Alopecia results from a failure to terminate hair development properly, as hair clubs never form, and follicular retraction is slowed. Hair regeneration is rapid due to premature activation of new hair-production programs. Hair shafts differentiate aberrantly due to impaired arrest of medullary-cell proliferation. When Bmpr2/Acvr2a function is reduced in melanocytes, gray hair develops, as melanosomes differentiate but fail to grow, resulting in organelle miniaturization. We conclude that Bmpr2 and Acvr2a normally play cell-type-specific, necessary roles in organelle biogenesis and the shutdown of developmental programs and cell division. PMID:22611050

Blockade of S100A3 activity inhibits murine hair growth.

PubMed

Guan, W; Deng, Q; Yu, X L; Yuan, Y S; Gao, J; Li, J J; Zhou, L; Xia, P; Han, G Y Q; Han, W; Yu, Y

2015-10-28

Using mouse gene expression microarray analysis, we obtained dynamic expression profiles of the whole genome in a depilation-induced hair growth mouse model. S100A3 expression increased during the anagen phase and returned to normal during the telogen phase. The effects of S100A3 blockade on the hair growth cycle were examined in mice after subcutaneous injection of an anti-mouse S100A3 antibody. Protein localization of S100A3 was confined to the hair shafts during the anagen phase and the sebaceous glands during the telogen phase. S100A3 blockade delayed hair follicle entry into the anagen phase, decreased hair elongation, and reduced the number of hair follicles in the subcutis, which correlated with the downregulated expression of hair growth induction-related genes in vivo. The present study demonstrates that anti-S100A3 antibody inhibits mouse hair growth, suggesting that S100A3 can be used as a target for hair loss treatment.

Hair growth induction by substance P.

PubMed

Paus, R; Heinzelmann, T; Schultz, K D; Furkert, J; Fechner, K; Czarnetzki, B M

1994-07-01

In vitro, some neuropeptides, including the tachykinin, substance P (SP), act as growth factors. The cyclic growth of the richly innervated hair follicle offers a model for probing such functions in a complex, developmentally regulated tissue interaction system under physiologic conditions. Dissecting the role of neuropeptides in this system may also reveal as yet obscure neural mechanisms of hair growth control. The neuropeptide-releasing neurotoxin, capsaicin was injected intradermally, or SP slow-release formulations were implanted subcutaneously in the back skin of C57BL/6 mice with all follicles in the resting stage of the hair cycle (telogen) in order to see whether this induced hair growth (anagen). In addition, the endogenous SP skin concentration and the activity of the main SP-degrading enzyme, neutral endopeptidase, were determined during the induced murine hair cycle by high performance liquid chromatography-controlled radioimmuno-assay (SP) or by fluorometry (neutral endopeptidase). Both capsaicin and SP induced significant hair growth (anagen) in the back skin of telogen mice. This was associated with substantial mast cell degranulation. The endogenous SP skin concentration showed significant, hair cycle-dependent fluctuations during the induced murine hair cycle, which were largely independent of the activity of neutral endopeptidase. SP may play a role in the neural control of hair growth. Whereas this pilot study does not address the underlying mechanisms of action, it demonstrates that SP has potential as a hair growth-stimulatory agent in vivo, and serves as a basis for exploring the role of tachykinins in epithelial-mesenchymal-neuroectodermal interaction systems like the hair follicle.

A role of placental growth factor in hair growth.

PubMed

Yoon, Sun-Young; Yoon, Ji-Seon; Jo, Seong Jin; Shin, Chang Yup; Shin, Jong-Yeon; Kim, Jong-Il; Kwon, Ohsang; Kim, Kyu Han

2014-05-01

The dermal papilla (DP) comprises specialized mesenchymal cells at the bottom of the hair follicle and plays a pivotal role in hair formation, anagen induction and the hair cycle. In this study, DPs were isolated from human hair follicles and serially subcultured. From each subculture at passages 1, 3, and 5 (n=4), we compared gene expression profiles using mRNA sequencing. Among the growth factors that were down-regulated in later passages of human DP cells (hDPCs), placental growth factor (PlGF) was selected. To elucidate the effect of PlGF on hair growth. We evaluated the effect of PlGF on hDPCs and on ex vivo hair organ culture. We investigated the effect of PlGF on an in vivo model of depilation-induced hair regeneration. We confirmed that the mRNA and protein expression levels of PlGF significantly decreased following subculture of the cells. It was shown that PlGF enhanced hair shaft elongation in ex vivo hair organ culture. Furthermore, PlGF significantly accelerated hair follicle growth and markedly prolonged anagen hair growth in an in vivo model of depilation-induced hair regeneration. PlGF prevented cell death by increasing the levels of phosphorylated extracellular signal-regulated kinase (ERK) and cyclin D1 and promoted survival by up-regulation of phosphorylated Akt and Bcl2, as determined by Western blotting. Our results suggest that PlGF plays a role in the promotion of hair growth and therefore may serve as an additional therapeutic target for the treatment of alopecia. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

In vivo evaluation of insect wax for hair growth potential.

PubMed

Ma, Jinju; Ma, Liyi; Zhang, Zhongquan; Li, Kai; Wang, Youqiong; Chen, Xiaoming; Zhang, Hong

2018-01-01

Insect wax is secreted by Ericerus pela Chavanness. It has been traditionally used to treat hair loss in China, but few reports have been published on the hair growth-promoting effect of insect wax. In this work, we examined the hair growth-promoting effects of insect wax on model animals. Different concentrations of insect wax were topically applied to the denuded backs of mice, and 5% minoxidil was applied topically as a positive control. We found that insect wax significantly promoted hair growth in a dose-dependent manner, 45% and 30% insect wax both induced hair to regrow, while less visible hair growth was observed in blank controls on the 16th day. The experimental areas treated with 45% and 30% insect wax exhibited significant differences in hair scores compared to blank controls, and hair lengths in the 45% and 30% insect wax group was significantly longer than in blank controls on the 16th and 20th days. There were no new hair follicles forming in the treated areas, and the hair follicles were prematurely converted to the anagen phase from the telogen phase in experimental areas treated with 45% and 30% insect wax. Both 45% and 30% insect wax upregulated vascular endothelial growth factor expression. The results indicated that 45% and 30% insect wax showed hair growth-promoting potential approximately as potent as 5% minoxidil by inducing the premature conversion of telogen-to-anagen and by prolonging the mature anagen phase rather than increasing the number of hair follicles, which was likely related to the upregulation of VEGF expression. The dissociative policosanol in insect wax was considered the key ingredient most likely responsible for the hair growth promoting potential.

In vivo evaluation of insect wax for hair growth potential

PubMed Central

Ma, Jinju

2018-01-01

Insect wax is secreted by Ericerus pela Chavanness. It has been traditionally used to treat hair loss in China, but few reports have been published on the hair growth-promoting effect of insect wax. In this work, we examined the hair growth-promoting effects of insect wax on model animals. Different concentrations of insect wax were topically applied to the denuded backs of mice, and 5% minoxidil was applied topically as a positive control. We found that insect wax significantly promoted hair growth in a dose-dependent manner, 45% and 30% insect wax both induced hair to regrow, while less visible hair growth was observed in blank controls on the 16th day. The experimental areas treated with 45% and 30% insect wax exhibited significant differences in hair scores compared to blank controls, and hair lengths in the 45% and 30% insect wax group was significantly longer than in blank controls on the 16th and 20th days. There were no new hair follicles forming in the treated areas, and the hair follicles were prematurely converted to the anagen phase from the telogen phase in experimental areas treated with 45% and 30% insect wax. Both 45% and 30% insect wax upregulated vascular endothelial growth factor expression. The results indicated that 45% and 30% insect wax showed hair growth-promoting potential approximately as potent as 5% minoxidil by inducing the premature conversion of telogen-to-anagen and by prolonging the mature anagen phase rather than increasing the number of hair follicles, which was likely related to the upregulation of VEGF expression. The dissociative policosanol in insect wax was considered the key ingredient most likely responsible for the hair growth promoting potential. PMID:29438422

Trichostasis spinulosa of the scalp mimicking Alopecia Areata black dots*

PubMed Central

Chagas, Flavianne Sobral Cardoso; Donati, Aline; Soares, Isabella Ibrahim Doche; Valente, Neusa Sakai; Romiti, Ricardo

2014-01-01

Alopecia areata is a common autoimmune disorder that leads to nonscarring hair loss. Black dots, also called comedo-like cadaver hairs, can be found in almost 50% of alopecia areata patients and indicate disease activity. Trichostasis spinulosa is a follicular disorder resulting from the retention of numerous hairs surrounded by a keratinous sheath in dilated follicles. Trichostasis spinulosa is a relatively common but underdiagnosed disorder of hair follicles. Here, we describe a man with alopecia areata of the eyebrows, androgenetic alopecia and trichostasis spinulosa at the vertex and show how dermoscopy can be useful in distinguishing black dots from Trichostasis spinulosa lesions. PMID:25054768

Histogenesis of pure and combined Merkel cell carcinomas: An immunohistochemical study of 14 cases.

PubMed

Narisawa, Yutaka; Koba, Shinichi; Inoue, Takuya; Nagase, Kotaro

2015-05-01

The histogenesis of Merkel cell carcinoma (MCC) has remained unresolved. Moreover, one of the questions is whether pure MCC and combined MCC represent the same histogenesis and entity. The existence of combined MCC suggests that MCC likely arise from pluripotent stem cells. Merkel cells (MC) localize within the bulge area, which is populated by hair follicle stem cells. We used hair follicle stem cell markers to investigate whether MCC share certain characteristics of these stem cells. Fourteen MCC specimens were examined histologically and immunohistochemically. There were six pure MCC and eight combined MCC. In six combined MCC, both MCC components and squamous components at least focally shared the expression of one or more of cytokeratin (CK)15, CK19 and CD200, which are hair follicle stem cell markers. On the other hand, four cases of pure MCC showed partially distinct CK19 expression, but did not show CK15 and/or CD200 expression. There was a distinct difference between pure MCC and combined MCC on the expression of hair follicle stem cell markers. The normal skin expressed CK15, CK19 and CD200 in the bulge area, whereas CK15 and CD200 were absent in the MC-rich glabrous skin and touch domes. The results led us to hypothesize that combined MCC originate from the hair follicle stem cells. We postulate that combined MCC undergo multidirectional differentiation into squamous, glandular, mesenchymal and Merkel cells. Further investigation is warranted to confirm the histogenesis of pure MCC and combined MCC. © 2015 Japanese Dermatological Association.

Identification of Differentially Expressed miRNAs between White and Black Hair Follicles by RNA-Sequencing in the Goat (Capra hircus)

PubMed Central

Wu, Zhenyang; Fu, Yuhua; Cao, Jianhua; Yu, Mei; Tang, Xiaohui; Zhao, Shuhong

2014-01-01

MicroRNAs (miRNAs) play a key role in many biological processes by regulating gene expression at the post-transcriptional level. A number of miRNAs have been identified from livestock species. However, compared with other animals, such as pigs and cows, the number of miRNAs identified in goats is quite low, particularly in hair follicles. In this study, to investigate the functional roles of miRNAs in goat hair follicles of goats with different coat colors, we sequenced miRNAs from two hair follicles samples (white and black) using Solexa sequencing. A total of 35,604,016 reads were obtained, which included 30,878,637 clean reads (86.73%). MiRDeep2 software identified 214 miRNAs. Among them, 205 were conserved among species and nine were novel miRNAs. Furthermore, DESeq software identified six differentially expressed miRNAs. Quantitative PCR confirmed differential expression of two miRNAs, miR-10b and miR-211. KEGG pathways were analyzed using the DAVID website for the predicted target genes of the differentially expressed miRNAs. Several signaling pathways including Notch and MAPK pathways may affect the process of coat color formation. Our study showed that the identified miRNAs might play an essential role in black and white follicle formation in goats. PMID:24879525

Adapalene microemulsion for transfollicular drug delivery.

PubMed

Bhatia, Gaurav; Zhou, Yingcong; Banga, Ajay K

2013-08-01

The aim of this study was to develop a microemulsion formulation of adapalene for transfollicular delivery. A pseudoternary phase diagram was developed for microemulsion consisting of oleic acid as oil phase, tween 20 as surfactant, Transcutol® as cosurfactant, and deionized water. Differential tape stripping and confocal laser scanning microscopy were performed to determine the penetration of microemulsion through hair follicles. Transmission electron microscopy, dynamic light scattering, polarizing light microscopy, and differential scanning calorimetry were performed to characterize the microstructures of microemulsion. The pH and viscosity of the microemulsions were also determined. Permeation studies were carried out in vitro on porcine ear skin over a period of 24 h using Franz diffusion cells. The drug penetration in the hair follicles increased from 0.109 ± 0.03 to 0.292 ± 0.094 μg, as the microstructure of microemulsion shifted from oil-in-water to bi-continuous, with increase in water content of microemulsion. Confocal laser scanning microscopy images suggested that hair follicles provided the path for transfollicular permeation of adapalene microemulsion. These results suggest that microemulsion penetrated through hair follicles and are promising for transfollicular drug delivery. Copyright © 2013 Wiley Periodicals, Inc.

In vivo investigation of the efficiency of a nanoparticle-emulsion containing polihexanide on the human skin.

PubMed

Ulmer, M; Patzelt, A; Vergou, T; Richter, H; Müller, G; Kramer, A; Sterry, W; Czaika, V; Lademann, J

2013-06-01

Skin antisepsis is a key element for the prevention of surgical site infections, as well as for infections after injection and punctures. Recent investigations have shown that about 25% of the resident bacterial flora of the human skin resides within the hair follicle. These findings strongly suggest that the skin appendages play the role of a bacterial reservoir. The bacteria within the hair follicles therefore may be the cause of endogenous germ repopulation after skin antisepsis, highlighting the need for new antiseptic formulations that can sufficiently penetrate into the hair follicles. Various experiments have found that nano-sized particles as well as oil-in-water emulsions are efficient carriers for substances into the hair follicles. In the present study, we investigated the in vivo antiseptic potential of the particle-associated and aqueous polihexanide on the human skin by monitoring bacterial growth after antisepsis over a period of 2.5h. The experiments suggest that the use of a particle-bound antiseptic can achieve a better and longer lasting antisepsis of the human skin than in non-particulate form. Copyright © 2012 Elsevier B.V. All rights reserved.

Foxp1 Regulates the Proliferation of Hair Follicle Stem Cells in Response to Oxidative Stress during Hair Cycling

PubMed Central

Zhao, Jianzhi; Li, Hanjun; Zhou, Rujiang; Ma, Gang; Dekker, Joseph D.; Tucker, Haley O.; Yao, Zhengju; Guo, Xizhi

2015-01-01

Hair follicle stem cells (HFSCs) in the bugle circularly generate outer root sheath (ORS) through linear proliferation within limited cycles during anagen phases. However, the mechanisms controlling the pace of HFSC proliferation remain unclear. Here we revealed that Foxp1, a transcriptional factor, was dynamically relocated from the nucleus to the cytoplasm of HFSCs in phase transitions from anagen to catagen, coupled with the rise of oxidative stress. Mass spectrum analyses revealed that the S468 phosphorylation of Foxp1 protein was responsive to oxidative stress and affected its nucleocytoplasmic translocation. Foxp1 deficiency in hair follicles led to compromised ROS accrual and increased HFSC proliferation. And more, NAC treatment profoundly elongated the anagen duration and HFSC proliferation in Foxp1-deficient background. Molecularly, Foxp1 augmented ROS levels through suppression of Trx1-mediated reductive function, thereafter imposing the cell cycle arrest by modulating the activity of p19/p53 pathway. Our findings identify a novel role for Foxp1 in controlling HFSC proliferation with cellular dynamic location in response to oxidative stress during hair cycling. PMID:26171970

Adamson's Fringe, Horatio George Adamson, and Kligman's Experiments and Observations on Tinea Capitis

PubMed Central

Joshi, Rajiv

2011-01-01

Adamson's fringe is located at the upper margin of the keratogenous zone of the hair follicle where the nucleated hair shaft cornifies completely and gets converted to hard anucleated keratin. It marks also the area of complete keratinization of the cuticle and Henle's layer of the inner root sheath and the beginning of the stem of the follicle. In Tinea capitis, dermatophytic infection of the hair shaft is restricted to this zone and the fungi do not penetrate further down the infected hair in the bulb of the follicle. The fungi in Adamson's words form “a fringe of mycelium surrounding the hair shaft and project below the lower margin of the sheath of spores around the root-stem.” Horatio George Adamson (1865--1955), a British dermatologist first described this phenomenon, in 1895, and this article describes Adamson's fringe with a short biography of Adamson and discusses Kligman's experiments and observations on Tinea capitis which validated the observations of Adamson and the concept of Adamson's Fringe and described the pathogenesis in Tinea capitis. PMID:21769230

RBM28, a protein deficient in ANE syndrome, regulates hair follicle growth via miR-203 and p63.

PubMed

Warshauer, Emily; Samuelov, Liat; Sarig, Ofer; Vodo, Dan; Bindereif, Albrecht; Kanaan, Moien; Gat, Uri; Fuchs-Telem, Dana; Shomron, Noam; Farberov, Luba; Pasmanik-Chor, Metsada; Nardini, Gil; Winkler, Eyal; Meilik, Benjamin; Petit, Isabelle; Aberdam, Daniel; Paus, Ralf; Sprecher, Eli; Nousbeck, Janna

2015-08-01

Alopecia-neurological defects-endocrinopathy (ANE) syndrome is a rare inherited hair disorder, which was shown to result from decreased expression of the RNA-binding motif protein 28 (RBM28). In this study, we attempted to delineate the role of RBM28 in hair biology. First, we sought to obtain evidence for the direct involvement of RBM28 in hair growth. When RBM28 was downregulated in human hair follicle (HF) organ cultures, we observed catagen induction and HF growth arrest, indicating that RBM28 is necessary for normal hair growth. We also aimed at identifying molecular targets of RBM28. Given that an RBM28 homologue was recently found to regulate miRNA biogenesis in C. elegans and given the known pivotal importance of miRNAs for proper hair follicle development, we studied global miRNA expression profile in cells knocked down for RBM28. This analysis revealed that RBM28 controls the expression of miR-203. miR-203 was found to regulate in turn TP63, encoding the transcription factor p63, which is critical for hair morphogenesis. In conclusion, RBM28 contributes to HF growth regulation through modulation of miR-203 and p63 activity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Red ginseng extract promotes the hair growth in cultured human hair follicles.

PubMed

Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun

2015-03-01

Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

Red Ginseng Extract Promotes the Hair Growth in Cultured Human Hair Follicles

PubMed Central

Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun

2015-01-01

Abstract Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans. PMID:25396716

Androgen regulation of the human hair follicle: the type I hair keratin hHa7 is a direct target gene in trichocytes.

PubMed

Jave-Suarez, Luis F; Langbein, Lutz; Winter, Hermelita; Praetzel, Silke; Rogers, Michael A; Schweizer, Juergen

2004-03-01

Previous work had shown that most members of the complex human hair keratin family were expressed in terminal scalp hairs. An exception to this rule was the type I hair keratin hHa7, which was only detected in some but not all vellus hairs of the human scalp (Langbein et al, 1999). Here we show that hHa7 exhibits constitutive expression in medullary cells of all types of male and female sexual hairs. Medullated beard, axillary, and pubic hairs arise during puberty from small, unmedullated vellus hairs under the influence of circulating androgens. This suggested an androgen-controlled expression of the hHa7 gene. Further evidence for this assumption was provided by the demonstration of androgen receptor (AR) expression in the nuclei of medullary cells of beard hairs. Moreover, homology search for the semipalindromic androgen receptor-binding element (ARE) consensus sequence GG(A)/(T)ACAnnnTGTTCT in the proximal hHa7 promoter revealed three putative ARE motifs. Electrophoretic mobility shift assays demonstrated the specific binding of AR to all three hHa7 AREs. Their function as AR-responsive elements, either individually or in concert within the hHa7 promoter, could be further confirmed by transfection studies with or without an AR expression vector in PtK2 and prostate PC3-Arwt cells, respectively in the presence or absence of a synthetic androgen. Our study detected hHa7 as the first gene in hair follicle trichocytes whose expression appears to be directly regulated by androgens. As such, hHa7 represents a marker for androgen action on hair follicles and might be a suitable tool for investigations of androgen-dependent hair disorders.

Fibroblast Growth Factors Stimulate Hair Growth through β-Catenin and Shh Expression in C57BL/6 Mice

PubMed Central

Lin, Wei-hong; Xiang, Li-Jun; Shi, Hong-Xue; Zhang, Jian; Jiang, Li-ping; Cai, Ping-tao; Lin, Zhen-Lang; Lin, Bei-Bei; Huang, Yan; Zhang, Hai-Lin; Fu, Xiao-Bing; Guo, Ding-Jiong; Li, Xiao-Kun; Wang, Xiao-Jie; Xiao, Jian

2015-01-01

Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of β-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent. PMID:25685806

Does D matter? The role of vitamin D in hair disorders and hair follicle cycling.

PubMed

Amor, Karrie T; Rashid, Rashid M; Mirmirani, Paradi

2010-02-15

The role of vitamin D in the proliferation and differentiation of keratinocytes is well known within the field of dermatology. We sought to evaluate the role that vitamin D and the vitamin D receptor play in the hair cycle and assess how this can be clinically applied to the treatment of hair disorders. A MEDLINE search (1955-July 2009) was preformed to find relevant articles pertaining to vitamin D, the vitamin D receptor, and hair loss. The vitamin D receptor, independent of vitamin D, plays an important role in hair cycling, specifically anagen initiation. The role of vitamin D in hair follicle cycling is not as well understood. The review is broad and there are limited human studies available to date. Additional studies to evaluate the role of vitamin D in the hair cycle should be done. Treatments that up regulate the vitamin D receptor may be successful in treating hair disorders and are a potential area of further study.

Color-dilution alopecia in dogs.

PubMed

Kim, Jae Hoon; Kang, Kyung Il; Sohn, Hyun Joo; Woo, Gye Hyeong; Jean, Young Hwa; Hwang, Eui Kyung

2005-09-01

Color-dilution alopecia is a relatively uncommon hereditary skin disease seen in "Blue" and other color-diluted dogs. This syndrome is associated with a color-dilution gene. The initial clinical signs are the gradual onset of a dry, dull and poor hair coat quality. Hair shafts and hair regrowth are poor, and follicular papules may develop and progress to frank comedones. Hair loss and comedo formation are usually most severe on the trunk, especially color-diluted area on the skin. Six cases of color-dilution alopecia are reported in 3 months to 10 years old dogs. The breeds of dogs are blue Doberman Pinscher, Miniature Pinscher, Dachshund, and Schnauzer. Grossly, extensive partial hair loss was seen on the skin. Histopathologically, the epidermis is relatively normal but may be hyperplastic. Hair follicles are characterized by atrophy and distortion. Heavily clumped melanin is present in the epidermis, dermis and hair follicles.

Congenital panfollicular nevus associated with polydactyly.

PubMed

Kim, Jinah; Zambrano, Eduardo V; McNiff, Jennifer M

2007-12-01

A 2-year-old girl presented with ulnar-sided duplication of the left thumb distal to the interphalangeal joint and syndactyly of the first web space. She also had several asymptomatic pink-tan cutaneous papules, involving the first and second ray of the left hand and wrist, clinically resembling a linear epidermal nevus. Microscopically, the papules were composed of well-circumscribed aggregates of basaloid epithelium within the dermis. No normal hair follicles were identified. Follicular germ and papillae were identified, representing abortive attempts at hair follicle formation. The features were remarkably similar to a novel entity described by Finn and Argenyi as congenital panfollicular nevus. In our case, the congenital panfollicular nevus was associated with distal thumb polysyndactyly, which may suggest an important link between limb patterning and hair follicle development.

Molecular Dissection of Mesenchymal–Epithelial Interactions in the Hair Follicle

PubMed Central

Rendl, Michael; Lewis, Lisa

2005-01-01

De novo hair follicle formation in embryonic skin and new hair growth in adult skin are initiated when specialized mesenchymal dermal papilla (DP) cells send cues to multipotent epithelial stem cells. Subsequently, DP cells are enveloped by epithelial stem cell progeny and other cell types to form a niche orchestrating hair growth. Understanding the general biological principles that govern the mesenchymal–epithelial interactions within the DP niche, however, has been hampered so far by the lack of systematic approaches to dissect the complete molecular make-up of this complex tissue. Here, we take a novel multicolor labeling approach, using cell type–specific transgenic expression of red and green fluorescent proteins in combination with immunolabeling of specific antigens, to isolate pure populations of DP and four of its surrounding cell types: dermal fibroblasts, melanocytes, and two different populations of epithelial progenitors (matrix and outer root sheath cells). By defining their transcriptional profiles, we develop molecular signatures characteristic for the DP and its niche. Validating the functional importance of these signatures is a group of genes linked to hair disorders that have been largely unexplored. Additionally, the DP signature reveals novel signaling and transcription regulators that distinguish them from other cell types. The mesenchymal–epithelial signatures include key factors previously implicated in ectodermal-neural fate determination, as well as a myriad of regulators of bone morphogenetic protein signaling. These findings establish a foundation for future functional analyses of the roles of these genes in hair development. Overall, our strategy illustrates how knowledge of the genes uniquely expressed by each cell type residing in a complex niche can reveal important new insights into the biology of the tissue and its associated disease states. PMID:16162033

Depositing α-mangostin nanoparticles to sebaceous gland area for acne treatment.

PubMed

Pan-In, Porntip; Wongsomboon, Atthakorn; Kokpol, Chayada; Chaichanawongsaroj, Nuntaree; Wanichwecharungruang, Supason

2015-12-01

Although entrapment of nanoparticles of appropriate sizes at hair follicles has been clarified, there is no report on specific clinical application of this finding. Since sebaceous gland is associated with hair follicle, we hypothesize that effective acne vulgaris treatment/prevention can be achieved by depositing anti-acne agent in nanoparticle form at the hair follicles. Challenge of this strategy, however, lies at the finding of effective anti-acne particles with minimal skin irritation. Here using cellulose-based nanoparticles as nano-reservoir and α-mangostin (an active component isolated from the edible Garcinia mangostana Linn. fruit) as anti-acne agent, we prepare nanoparticles highly loaded with α-mangostin. Ability of the obtained particles to sustained release α-mangostin into synthetic sebum is demonstrated. The obtained mangostin particles are verified for their insignificant skin irritation through the two-week, twice-daily open application test in 20 healthy human volunteers. Excellent entrapment and sustainment of the mangostin nanoparticles at the hair follicles are elucidated in six human volunteers by detecting the presence of α-mangostin at the roots of hairs pulled from the treated skin area. The 4-week-randomized, double-blind, placebo-controlled, split-face study in 10 acne patients indicates significant improvement in acne vulgaris condition on the side twice daily applied with mangostin nanoparticles. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Normal and aging hair biology and structure 'aging and hair'.

PubMed

Goodier, Molly; Hordinsky, Maria

2015-01-01

Much like an individual's hairstyle, hair fibers along the scalp see a number of changes over the course of one's lifetime. As the decades pass, the shine and volume synonymous with youthful hair may give way to thin, dull, and brittle hair commonly associated with aging. These changes are a result of a compilation of genetic and environmental elements influencing the cells of the hair follicle, specifically the hair follicle stem cells and melanocytes. Telomere shortening, decrease in cell numbers, and particular transcription factors have all been implicated in this process. In turn, these molecular alterations lead to structural modifications of the hair fiber, decrease in melanin production, and lengthening of the telogen phase of the hair cycle. Despite this inevitable progression with aging, there exists an array of treatments such as light therapy, minoxidil, and finasteride which have been designed to mitigate the effects of aging, particularly balding and thinning hair. Although each works through a different mechanism, all aim to maintain or potentially restore the youthful quality of hair. © 2015 S. Karger AG, Basel.

Cornu cervi pantotrichum Pharmacopuncture Solution Facilitate Hair Growth in C57BL/6 Mice

PubMed Central

Lee, Seon-Yong; Lee, Dong-Jin; Kwon, Kang; Lee, Chang-Hyun; Shin, Hyun Jong; Kim, Jai Eun; Ha, Ki-Tae; Jeong, Han-Sol

2016-01-01

Objectives: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. Methods: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. Results: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. Conclusion: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up-regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia. PMID:27386145

Doppler laser imaging predicts response to topical minoxidil in the treatment of female pattern hair loss.

PubMed

McCoy, J; Kovacevic, M; Situm, M; Stanimirovic, A; Bolanca, Z; Goren, A

2016-01-01

Topical minoxidil is the only drug approved by the US FDA for the treatment of female pattern hair loss. Unfortunately, following 16 weeks of daily application, less than 40% of patients regrow hair. Several studies have demonstrated that sulfotransferase enzyme activity in plucked hair follicles predicts topical minoxidil response in female pattern hair loss patients. However, due to patients’ discomfort with the procedure, and the time required to perform the enzymatic assay it would be ideal to develop a rapid, non-invasive test for sulfotransferase enzyme activity. Minoxidil is a pro-drug converted to its active form, minoxidil sulfate, by sulfotransferase enzymes in the outer root sheath of hair. Minoxidil sulfate is the active form required for both the promotion of hair regrowth and the vasodilatory effects of minoxidil. We thus hypothesized that laser Doppler velocimetry measurement of scalp blood perfusion subsequent to the application of topical minoxidil would correlate with sulfotransferase enzyme activity in plucked hair follicles. In this study, plucked hair follicles from female pattern hair loss patients were analyzed for sulfotransferase enzyme activity. Additionally, laser Doppler velocimetry was used to measure the change in scalp perfusion at 15, 30, 45, and 60 minutes, after the application of minoxidil. In agreement with our hypothesis, we discovered a correlation (r=1.0) between the change in scalp perfusion within 60 minutes after topical minoxidil application and sulfotransferase enzyme activity in plucked hairs. To our knowledge, this is the first study demonstrating the feasibility of using laser Doppler imaging as a rapid, non-invasive diagnostic test to predict topical minoxidil response in the treatment of female pattern hair loss.

Differential effects of caffeine on hair shaft elongation, matrix and outer root sheath keratinocyte proliferation, and transforming growth factor-β2/insulin-like growth factor-1-mediated regulation of the hair cycle in male and female human hair follicles in vitro.

PubMed

Fischer, T W; Herczeg-Lisztes, E; Funk, W; Zillikens, D; Bíró, T; Paus, R

2014-11-01

Caffeine reportedly counteracts the suppression of hair shaft production by testosterone in organ-cultured male human hair follicles (HFs). We aimed to investigate the impact of caffeine (i) on additional key hair growth parameters, (ii) on major hair growth regulatory factors and (iii) on male vs. female HFs in the presence of testosterone. Microdissected male and female human scalp HFs were treated in serum-free organ culture for 120 h with testosterone alone (0·5 μg mL(-1)) or in combination with caffeine (0·005-0·0005%). The following effects on hair shaft elongation were evaluated by quantitative (immuno)histomorphometry: HF cycling (anagen-catagen transition); hair matrix keratinocyte proliferation; expression of a key catagen inducer, transforming growth factor (TGF)-β2; and expression of the anagen-prolonging insulin-like growth factor (IGF)-1. Caffeine effects were further investigated in human outer root sheath keratinocytes (ORSKs). Caffeine enhanced hair shaft elongation, prolonged anagen duration and stimulated hair matrix keratinocyte proliferation. Female HFs showed higher sensitivity to caffeine than male HFs. Caffeine counteracted testosterone-enhanced TGF-β2 protein expression in male HFs. In female HFs, testosterone failed to induce TGF-β2 expression, while caffeine reduced it. In male and female HFs, caffeine enhanced IGF-1 protein expression. In ORSKs, caffeine stimulated cell proliferation, inhibited apoptosis/necrosis, and upregulated IGF-1 gene expression and protein secretion, while TGF-β2 protein secretion was downregulated. This study reveals new growth-promoting effects of caffeine on human hair follicles in subjects of both sexes at different levels (molecular, cellular and organ). © 2014 British Association of Dermatologists.

External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.

PubMed

Fan, Sabrina Mai-Yi; Chang, Yi-Ting; Chen, Chih-Lung; Wang, Wei-Hung; Pan, Ming-Kai; Chen, Wen-Pin; Huang, Wen-Yen; Xu, Zijian; Huang, Hai-En; Chen, Ting; Plikus, Maksim V; Chen, Shih-Kuo; Lin, Sung-Jan

2018-06-29

Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.

Counter-rotational cell flows drive morphological and cell fate asymmetries in mammalian hair follicles.

PubMed

Cetera, Maureen; Leybova, Liliya; Joyce, Bradley; Devenport, Danelle

2018-05-01

Organ morphogenesis is a complex process coordinated by cell specification, epithelial-mesenchymal interactions and tissue polarity. A striking example is the pattern of regularly spaced, globally aligned mammalian hair follicles, which emerges through epidermal-dermal signaling and planar polarized morphogenesis. Here, using live-imaging, we discover that developing hair follicles polarize through dramatic cell rearrangements organized in a counter-rotational pattern of cell flows. Upon hair placode induction, Shh signaling specifies a radial pattern of progenitor fates that, together with planar cell polarity, induce counter-rotational rearrangements through myosin and ROCK-dependent polarized neighbour exchanges. Importantly, these cell rearrangements also establish cell fate asymmetry by repositioning radial progenitors along the anterior-posterior axis. These movements concurrently displace associated mesenchymal cells, which then signal asymmetrically to maintain polarized cell fates. Our results demonstrate how spatial patterning and tissue polarity generate an unexpected collective cell behaviour that in turn, establishes both morphological and cell fate asymmetry.

In vivo hair growth promotion effects of ultra-high molecular weight poly-γ-glutamic acid from Bacillus subtilis (Chungkookjang).

PubMed

Choi, Jae-Chul; Uyama, Hiroshi; Lee, Chul-Hoon; Sung, Moon-Hee

2015-03-01

We investigated the effect of ultra-high molecular weight poly-γ-glutamic acid (UHMW γ-PGA) on hair loss in vitro and in vivo. 5-Alpha reductase is an enzyme that metabolizes the male hormone testosterone into dihydrotestosterone. By performing an in vitro experiment to analyze the inhibitory effects of UHMW γ-PGA on 5-alpha reductase activity, we determined that UHMW γ-PGA did in fact inhibit 5-alpha reductase activity, indicating the use of UHMW γ-PGA as a potential 5-alpha reductase inhibitor in the treatment of men with androgenetic alopecia. To evaluate the promotion of hair growth in vivo, we topically applied UHMW γ-PGA and minoxidil on the shaved dorsal skin of telogenic C57BL/6 mice for 4 weeks. At 4 weeks, the groups treated with UHMW γ-PGA showed hair growth on more than 50% of the shaved skin, whereas the control group showed less hair growth. To investigate the progression of hair follicles in the hair cycle, hematoxylin and eosin staining was performed. Histological observations revealed that the appearance of hair follicles was earlier in the UHMW γ-PGA-treated group than in the control group. The number of hair follicles on the relative area of shaved skin in the UHMW γ-PGA-treated group was higher than that observed on the shaved skin in the control group. These results indicate that UHMW γ-PGA can promote hair growth by effectively inducing the anagen phase in telogenic C57BL/6 mice.

Ultra-structural hair alterations in Friedreich's ataxia: A scanning electron microscopic investigation.

PubMed

Turkmenoglu, F Pinar; Kasirga, U Baran; Celik, H Hamdi

2015-08-01

Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder involving progressive damage to the central and peripheral nervous systems and cardiomyopathy. FRDA is caused by the silencing of the FXN gene and reduced levels of the encoded protein, frataxin. Frataxin is a mitochondrial protein that functions primarily in iron-sulfur cluster synthesis. Skin disorders including hair abnormalities have previously been reported in patients with mitochondrial disorders. However, to our knowledge, ultra-structural hair alterations in FRDA were not demonstrated. The purpose of this study was to determine ultra-structural alterations in the hairs of FRDA patients as well as carriers. Hair specimen from four patients, who are in different stages of the disease, and two carriers were examined by scanning electron microscope. Thin and weak hair follicles with absence of homogeneities on the cuticular surface, local damages of the cuticular layer, cuticular fractures were detected in both carriers and patients, but these alterations were much more prominent in the hair follicles of patients. In addition, erosions on the surface of the cuticle and local deep cavities just under the cuticular level were observed only in patients. Indistinct cuticular pattern, pores on the cuticular surface, and presence of concavities on the hair follicle were also detected in patients in later stages of the disease. According to our results, progression of the disease increased the alterations on hair structure. We suggest that ultra-structural alterations observed in hair samples might be due to oxidative stress caused by deficient frataxin expression in mitochondria. © 2015 Wiley Periodicals, Inc.

Adenovirus-mediated Wnt5a expression inhibits the telogen-to-anagen transition of hair follicles in mice.

PubMed

Xing, Yi-Zhan; Wang, Rui-Min; Yang, Ke; Guo, Hai-Ying; Deng, Fang; Li, Yu-Hong; Ye, Ji-Xing; He, Long; Lian, Xiao-Hua; Yang, Tian

2013-01-01

The canonical Wnt/β-catenin pathway plays an important role in hair cycle induction. Wnt5a is a non-canonical Wnt family member that generally antagonizes canonical Wnt signaling in other systems. In hair follicles, Wnt5a and canonical Wnt are both expressed in cells in the telogen stage. Wnt5a has been shown to be critical for controlling hair cell fate. However, the role that Wnt5a plays in the transition from the telogen to anagen stage is unknown. In this study, using whole-mount in situ hybridization, we show that Wnt5a is produced by several other cell types, excluding dermal papilla cells, throughout the hair cycle. For example, Wnt5a is expressed in bulge and secondary hair germ cells in the telogen stage. Our studies focused on the depilated 8-week-old mouse as a synchronized model of hair growth. Interestingly, overexpression of adenovirus Wnt5a in the dorsal skin of mice led to the elongation of the telogen stage and inhibition of the initiation of the anagen stage. However, following an extended period of time, four pelage hair types grew from hairless skin that was induced by Wnt5a, and the structure of these new hair shafts was normal. Using microarray analysis and quantitative arrays, we showed that the expression of β-catenin and some target genes of canonical Wnt signaling decreased after Wnt5a treatment. These data demonstrate that Wnt5a may inhibit the telogen stage to maintain a quiescent state of the hair follicle.

Human dermal papilla cells and outer root sheath cells: no follicular differentiation in nude mice and chicken embryos.

PubMed

Chiu, H C; Chang, C H; Jee, S H; Chang, C C; Wu, Y C

1994-09-01

Human scalp specimens were incubated in 5 U/ml dispase solution at 4 degrees C overnight before the isolation of dermal papillae and follicle epithelium. This pretreatment not only facilitated the attachment and cell outgrowth of dermal papillae but also made it easier to pluck out hairs with intact follicle epithelium. The outer root sheath cells were released from the follicle epithelium and grown on a feeder layer of mitomycin C-treated human dermal fibroblasts. The subcultured outer root sheath cells were grown in a serum-free medium. When the mixtures of early-passage dermal papilla cells and outer root sheath cells were injected into the subcutis of nude mice, an epidermal cyst surrounded by layers of fibrous tissue was found in three weeks. No hair follicles were found when the mixtures were implanted onto the chorioallantoic membrane of nine-day-old chicken embryos. A keratinized mass lying on the chorionic epithelium with or without smaller similar masses in the chorioallantoic membrane was found in eight days. No hair follicle-like structure could be found. Possible factors contributing to the failure to undergo follicular differentiation in this study are discussed.

Evaluation of the effect of formic acid and sodium formate on hair reduction in rat

PubMed Central

Banihashemi, Mahnaz; Rad, Abolfazl Khajavi; Yazdi, Seyed Abbas Tabatabaee; Rakhshande, Hasan; Ghoyonlo, Vahid Mashayekhi; Zabihi, Zahra; Yousefzadeh, Hadis

2011-01-01

Hirsutism is a common problem in dermatology that imposes high socioeconomical costs on medical care. Consequently, researchers are actively searching for cheaper and safer methods for therapeutic treatment. The objective of the present study is to evaluate formic oil, enriched from formic acid, for the removal of unwanted hair. In this study, 32 female rats (150–200 g) were randomly divided into four groups and maintained with normal water and food availability. A patch of skin was shaved on each rat for application of test solutions. The control group was treated with local once-daily applications of normal saline. The formic acid, acetic acid, and sodium formate groups were treated with once-daily applications of formic acid (pH 5.5), acetic acid (pH 5.5), or sodium formate, respectively. After 2 weeks, horizontally cut sample biopsies were removed, and the numbers of hair follicles were counted under high field microscopy by a specialist blinded to the treatments. Kolmogorov–Smirnov test results indicated a nonparametric distribution for the rat groups. ANOVA analysis indicated no statistically significant differences between groups (P < 0.05). There weren’t any side effects or evidence for toxicity during the study period. However, hair follicle counts showed a descending order of control, acetic acid, formic acid, and sodium formate. Although the sodium formate group had the lowest hair follicle numbers, the difference was not statistically significant (P > 0.05). Formic acid was not effective in reducing hair follicle numbers in rats. PMID:21760741

Stress and the Hair Growth Cycle: Cortisol-Induced Hair Growth Disruption.

PubMed

Thom, Erling

2016-08-01

The stress hormone, cortisol, is known to affect the function and cyclic regulation of the hair follicle. When cortisol is present at high levels it has been demonstrated to reduce the synthesis and accelerate the degradation of important skin elements, namely hyaluronan and proteoglycans by approximately 40%. The following discussion outlines the relationship between stress, cortisol, and the effect on the normal function of the hair follicle. As a result of this connection, important correlations have been established in the literature to form a basis for novel, effective treatments of stress-related hair growth disorders.
Amongst various treatment methods and substances, oral supplementation with a specific bioavailable proteoglycan stands out as a promising new therapeutic treatment method.

J Drugs Dermatol. 2016;15(8):1001-1004.

Improved Poly (D,L-lactide) nanoparticles-based formulation for hair follicle targeting.

PubMed

Fernandes, B; Silva, R; Ribeiro, A; Matamá, T; Gomes, A C; Cavaco-Paulo, A M

2015-06-01

Hair follicles are widely recognized as the preferential target and site of accumulation for nanoparticles after topical application. This feature is of particular importance for hair cosmetics, having the potential to refine the treatment of several hair follicle-related disorders. The aim of this work was to improve the preparation of Poly (D,L-lactide) (PLA) nanoparticles for in vivo follicular target and drug delivery. Envisaging a future industrial scale-up of the process, nanoprecipitation method was used to prepare PLA nanoparticles: the effect of several processing parameters on their properties was examined and the yield of nanoparticles formation determined. Encapsulation efficiencies and in vitro release profiles of lipophilic and hydrophilic model compounds were also assessed. In vitro cytotoxicity and ex vivo penetration studies were performed on a reference skin cell line (NCTC2455, human skin keratinocytes) and porcine skin, respectively. Using acetone : ethanol (50 : 50, v/v) as the solvent phase, 0.6% (w/w) of Pluronic(®) F68 as a surfactant agent and agitation to mix the solvent and non-solvent phases, a monodispersed population of non-cytotoxic spherical nanoparticles of approximately 150 nm was obtained. The yield of nanoparticles for this formulation was roughly 90%. After encapsulation of model compounds, no significant changes were found in the properties of particles and the entrapment efficiencies were above 80%. The release kinetics of dyes from PLA nanoparticles indicate an anomalous transport mechanism (diffusion and polymer degradation) for Nile Red (lipophilic) and a Fickian diffusion of first order for fluorescein 5(6)-isothiocyanate (hydrophilic). Ex vivo skin penetration studies confirmed the presence of nanoparticles along the entire follicular ducts. The optimized method allows the preparation of ideal PLA nanoparticles-based formulations for hair follicle targeting. PLA nanoparticles can effectively transport and release lipophilic and hydrophilic compounds into the hair follicles, and the yields obtained are acceptable for industrial purposes. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Ectopic Atoh1 expression drives Merkel cell production in embryonic, postnatal and adult mouse epidermis.

PubMed

Ostrowski, Stephen M; Wright, Margaret C; Bolock, Alexa M; Geng, Xuehui; Maricich, Stephen M

2015-07-15

Merkel cells are mechanosensitive skin cells whose production requires the basic helix-loop-helix transcription factor Atoh1. We induced ectopic Atoh1 expression in the skin of transgenic mice to determine whether Atoh1 was sufficient to create additional Merkel cells. In embryos, ectopic Atoh1 expression drove ectopic expression of the Merkel cell marker keratin 8 (K8) throughout the epidermis. Epidermal Atoh1 induction in adolescent mice similarly drove widespread K8 expression in glabrous skin of the paws, but in the whisker pads and body skin ectopic K8+ cells were confined to hair follicles and absent from interfollicular regions. Ectopic K8+ cells acquired several characteristics of mature Merkel cells in a time frame similar to that seen during postnatal development of normal Merkel cells. Although ectopic K8+ cell numbers decreased over time, small numbers of these cells remained in deep regions of body skin hair follicles at 3 months post-induction. In adult mice, greater numbers of ectopic K8+ cells were created by Atoh1 induction during anagen versus telogen and following disruption of Notch signaling by conditional deletion of Rbpj in the epidermis. Our data demonstrate that Atoh1 expression is sufficient to produce new Merkel cells in the epidermis, that epidermal cell competency to respond to Atoh1 varies by skin location, developmental age and hair cycle stage, and that the Notch pathway plays a key role in limiting epidermal cell competency to respond to Atoh1 expression. © 2015. Published by The Company of Biologists Ltd.

Regeneration of fat cells from myofibroblasts during wound healing.

PubMed

Plikus, Maksim V; Guerrero-Juarez, Christian F; Ito, Mayumi; Li, Yun Rose; Dedhia, Priya H; Zheng, Ying; Shao, Mengle; Gay, Denise L; Ramos, Raul; Hsi, Tsai-Ching; Oh, Ji Won; Wang, Xiaojie; Ramirez, Amanda; Konopelski, Sara E; Elzein, Arijh; Wang, Anne; Supapannachart, Rarinthip June; Lee, Hye-Lim; Lim, Chae Ho; Nace, Arben; Guo, Amy; Treffeisen, Elsa; Andl, Thomas; Ramirez, Ricardo N; Murad, Rabi; Offermanns, Stefan; Metzger, Daniel; Chambon, Pierre; Widgerow, Alan D; Tuan, Tai-Lan; Mortazavi, Ali; Gupta, Rana K; Hamilton, Bruce A; Millar, Sarah E; Seale, Patrick; Pear, Warren S; Lazar, Mitchell A; Cotsarelis, George

2017-02-17

Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro . Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans. Copyright © 2017, American Association for the Advancement of Science.

Overexpression of Wnt5a in mouse epidermis causes no psoriasis phenotype but an impairment of hair follicle anagen development.

PubMed

Zhu, Xuming; Wu, Yumei; Huang, Sixia; Chen, Yingwei; Tao, Yixin; Wang, Yushu; He, Shigang; Shen, Sanbing; Wu, Ji; Guo, Xizhi; Li, Baojie; He, Lin; Ma, Gang

2014-12-01

Increased Wnt5a expression has been observed in psoriatic plaques. However, whether Wnt5a overexpression directly causes psoriasis is unknown. In this study, we generated transgenic (TG) mice with epidermal Wnt5a overexpression under the control of the human K14 promoter. The skin of Wnt5a TG mice was not psoriatic, but characterized with normal proliferation and homeostasis of epidermis. Instead, these TG mice displayed impaired hair follicle transition from telogen to anagen, most likely due to impaired canonical Wnt signalling. These results suggest that increased Wnt5a expression alone is inadequate to induce psoriasis in the skin and possible involvement of Wnt5a in hair follicle cycling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ecklonia cava promotes hair growth.

PubMed

Bak, S S; Ahn, B N; Kim, J A; Shin, S H; Kim, J C; Kim, M K; Sung, Y K; Kim, S K

2013-12-01

Previous studies have reported the protective effects on skin elasticity of the edible marine seaweed Ecklonia cava, which acts through regulation of both antioxidative and anti-inflammatory responses. We evaluated the effect of E. cava and one of its components, dioxinodehydroeckol, on hair-shaft growth in cultured human hair follicles and on hair growth in mice. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to check cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells after treatment with E. cava and its metabolite, dioxinodehydroeckol. Hair-shaft growth was measured using the in vitro hair-follicle organ-culture system, in the presence or absence of E. cava and dioxinodehydroeckol. Anagen induction activity was examined by topical application of E. cava to the dorsal skin of C57BL/6 mice. Insulin-like growth factor (IGF)-1 expression was measured by reverse transcriptase PCR and ELISA. The proliferation activity was found to be highest for the ethyl acetate-soluble fraction of E. cava (EAFE) in DPCs and in ORS cells. Treatment with EAFE resulted in elongation of the hair shaft in cultured human hair follicles, and promoted transition of the hair cycle from the telogen to the anagen phase in the dorsal skin of C57BL/6 mice. In addition, EAFE induced an increase in IGF-1 expression in DPCs. Dioxinodehydroeckol, a component of E. cava, induced elongation of the hair shaft, an increase in proliferation of DPCs and ORS cells, and an increase in expression of IGF-1 in DPCs. These results suggest that E. cava containing dioxinodehydroeckol promotes hair growth through stimulation of DPCs and ORS cells. © 2013 British Association of Dermatologists.

Evaluation Indicators of Aesthetic Effects on Hair Transplantation.

PubMed

Miao, Yong; Liu, Bing-Cheng; Fan, Zhe-Xiang; Hu, Zhi-Qi

2016-02-01

Hair transplantation involves the transplantation of hair, beard, eyebrows, eyelashes, and pubic hair. Based on our experience, the aesthetic result of hair transplantation mainly relies on 4 indicators, including selection of the donor site, direction and angle of grafted hairs, density, and survival rate of implanted hair follicles. We believe that good results can be achieved as long as attention is paid to the above 4 points.

6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.

PubMed

Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

2013-01-01

Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal.

6-Gingerol Inhibits Hair Shaft Growth in Cultured Human Hair Follicles and Modulates Hair Growth in Mice

PubMed Central

Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

2013-01-01

Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal. PMID:23437345

Female pattern baldness

MedlinePlus

Alopecia in women; Baldness - female; Hair loss in women; Androgenetic alopecia in women; Hereditary balding or thinning in women ... Each strand of hair sits in a tiny hole (cavity) in the skin called a follicle. In general, baldness occurs when the hair ...

Hair cycle in dogs with different hair types in a tropical region of Brazil.

PubMed

Favarato, Evandro S; Conceição, Lissandro Gonçalves

2008-02-01

Hair cycle activity has been extensively studied in humans, sheep and laboratory animals, but there is a lack of information in dogs. Besides varying according to species, breed, sex and general health, hair growth is mainly affected by climatic variations. The aim of the study was to evaluate the follicle activity in three breeds of dogs with different hair types, in the city of Viçosa, Minas Gerais (latitude 20 degrees 45'S), Brazil. Twenty-one male dogs of boxer, labrador and schnauzer breeds were trichographically analysed monthly over 12 consecutive months. Hair percentage of telogen and anagen hairs at the different stages of the hair cycle in boxers and labradors was not significantly different, but both differed from the schnauzers. A significant correlation between hair follicle cycle and environmental temperature and photoperiod was noted in the boxers and labradors. In these breeds, a larger number of telogen hairs were observed during the hottest months of the year, and an increase in anagen hairs during the coldest months. The mean percentage of telogen hairs was 93, 90 and 55.3% for boxer, labrador and schnauzer, respectively.

Alterations in hair follicle dynamics in women.

PubMed

Piérard-Franchimont, Claudine; Piérard, Gérald E

2013-01-01

Endocrine changes supervening after parturition and menopause participate in the control of sebum production and hair growth modulation. The ensuing conditions include some peculiar aspects of hair loss (effluvium), alopecia, and facial hirsutism. The hair cycling is of major clinical relevance because most hair growth disorders result from disturbances in this chronobiological feature. Of note, any correlation between a biologic abnormality and hair cycling disturbance does not prove a relationship of causality. The proportion of postmenopausal women is rising in the overall population. Therefore, the prevalence of these hair follicle disturbances is globally on the rise. Current therapies aim at correcting the underlying hormonal imbalances, and at improving the overall cosmetic appearance. However, in absence of pathogenic diagnosis and causality criteria, chances are low that a treatment given by the whims of fate will adequately control hair effluvium. The risk and frequency of therapeutic inertia are further increased. When the hair loss is not controlled and/or compensated by growth of new hairs, several clinical aspects of alopecia inexorably develop. Currently, there is little evidence supporting any specific treatment for these endocrine hair disorders in post-partum and postmenopausal women. Current hair treatment strategies are symptomatic and nonspecific so current researchers aim at developing new, targeted methods.

Hair regrowth in alopecia areata patients following Stem Cell Educator therapy.

PubMed

Li, Yanjia; Yan, Baoyong; Wang, Hepeng; Li, Heng; Li, Quanhai; Zhao, Dong; Chen, Yana; Zhang, Ye; Li, Wenxia; Zhang, Jun; Wang, Shanfeng; Shen, Jie; Li, Yunxiang; Guindi, Edward; Zhao, Yong

2015-04-20

Alopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens. We have developed a Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the "educated" autologous cells to the patient's circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years). Clinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a "ring of transforming growth factor beta 1 (TGF-β1)" around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β(+)NKG2D(+) effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs. Current clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in subjects with moderate or severe AA. ClinicalTrials.gov, NCT01673789, 21 August 2012.

Primary Dermal Irritation Potential of Components of the M-258A-1 Decontamination Kit (Study 1).

DTIC Science & Technology

1981-09-01

cells and lymphocytes with an occasional heterophil in the connective tissue sheaths of a few hair follicles deep in the dermis. DX: Folliculitis ...acute, diffuse, mild to moderate, dermis, skin. DX: Folliculitis , subacute, multifocal, minimal, hair follicles, skin. Slide 4 - Skin: The entire skin...the dermis. DX: Hyperplasia, diffuse, moderate, epidermis, skin. DX: Degeneration, subacute, diffuse, minimal to mild, dermis, skin. DX: Folliculitis

LncRNAs in Secondary Hair Follicle of Cashmere Goat: Identification, Expression, and Their Regulatory Network in Wnt Signaling Pathway.

PubMed

Bai, Wen L; Zhao, Su J; Wang, Ze Y; Zhu, Yu B; Dang, Yun L; Cong, Yu Y; Xue, Hui L; Wang, Wei; Deng, Liang; Guo, Dan; Wang, Shi Q; Zhu, Yan X; Yin, Rong H

2018-07-03

Long noncoding RNAs (lncRNAs) are a novel class of eukaryotic transcripts. They are thought to act as a critical regulator of protein-coding gene expression. Herein, we identified and characterized 13 putative lncRNAs from the expressed sequence tags from secondary hair follicle of Cashmere goat. Furthermore, we investigated their transcriptional pattern in secondary hair follicle of Liaoning Cashmere goat during telogen and anagen phases. Also, we generated intracellular regulatory networks of upregulated lncRNAs at anagen in Wnt signaling pathway based on bioinformatics analysis. The relative expression of six putative lncRNAs (lncRNA-599618, -599556, -599554, -599547, -599531, and -599509) at the anagen phase is significantly higher than that at telogen. Compared with anagen, the relative expression of four putative lncRNAs (lncRNA-599528, -599518, -599511, and -599497) was found to be significantly upregulated at telogen phase. The network generated showed that a rich and complex regulatory relationship of the putative lncRNAs and related miRNAs with their target genes in Wnt signaling pathway. Our results from the present study provided a foundation for further elucidating the functional and regulatory mechanisms of these putative lncRNAs in the development of secondary hair follicle and cashmere fiber growth of Cashmere goat.

Iontophoresis-targeted, follicular delivery of minoxidil sulfate for the treatment of alopecia.

PubMed

Gelfuso, Guilherme Martins; Gratieri, Tais; Delgado-Charro, M Begoña; Guy, Richard H; Vianna Lopez, Renata Fonseca

2013-05-01

Although minoxidil (MX) is a drug known to stimulate hair growth, the treatment of androgenic alopecia could be improved by delivery strategies that would favor drug accumulation into the hair follicles. This work investigated in vitro the potential of iontophoresis to achieve this objective using MX sulfate (MXS), a more water-soluble derivative of MX. Passive delivery of MXS was first determined from an ethanol-water solution and from a thermosensitive gel. The latter formulation resulted in greater accumulation of MXS in the stratum corneum (skin's outermost layer) and hair follicles and an overall decrease in absorption through the skin. Anodal iontophoresis of MXS from the same gel formulation was then investigated at pH 3.5 and pH 5.5. Compared with passive delivery, iontophoresis increased the amount of drug reaching the follicular infundibula from 120 to 600 ng per follicle. In addition, drug recovery from follicular casts was threefold higher following iontophoresis at pH 5.5 compared with that at pH 3.5. Preliminary in vivo experiments in rats confirmed that iontophoretic delivery of MXS facilitated drug accumulation in hair follicles. Overall, therefore, iontophoresis successfully and significantly enhanced follicular delivery of MX suggesting a useful opportunity for the improved treatment of alopecia. Copyright © 2013 Wiley Periodicals, Inc.

Size-dependent penetration of nanoemulsions into epidermis and hair follicles: implications for transdermal delivery and immunization

PubMed Central

Su, Rui; Fan, Wufa; Yu, Qin; Dong, Xiaochun; Qi, Jianping; Zhu, Quangang; Zhao, Weili; Wu, Wei; Chen, Zhongjian; Li, Ye; Lu, Yi

2017-01-01

Nanoemulsions have been widely applied to dermal and transdermal drug delivery. However, whether and to what depth the integral nanoemulsions can permeate into the skin is not fully understood. In this study, an environment-responsive dye, P4, was loaded into nanoemulsions to track the transdermal translocation of the nanocarriers, while coumarin-6 was embedded to represent the cargoes. Particle size has great effects on the transdermal transportation of nanoemulsions. Integral nanoemulsions with particle size of 80 nm can diffuse into but not penetrate the viable epidermis. Instead, these nanoemulsions can efficiently fill the whole hair follicle canals and reach as deep as 588 μm underneath the dermal surfaces. The cargos are released from the nanoemulsions and diffuse into the surrounding dermal tissues. On the contrary, big nanoemulsions, with mean particle size of 500 nm, cannot penetrate the stratum corneum and can only migrate along the hair follicle canals. Nanoemulsions with median size, e.g. 200 nm, show moderate transdermal permeation effects among the three-size nanoemulsions. In addition, colocalization between nanoemulsions and immunofluorescence labeled antigen-presenting cells was observed in the epidermis and the hair follicles, implying possible capture of nanoemulsions by these cells. In conclusion, nanoemulsions are advantageous for transdermal delivery and potential in transcutaneous immunization. PMID:28465469

Effects of Topical Emu Oil on Burn Wounds in the Skin of Balb/c Mice

PubMed Central

Afshar, Mohammad; Ghaderi, Reza; Zardast, Mahmoud; Delshad, Parvin

2016-01-01

The goal of this study was to determine the effect of topical Emu oil on the healing of burn wounds and hair follicle restoration in superficial II-degree burns in the skin of Balb/c mice. Thirty-two male Balb/c mice with burns on the back of the neck were divided into two groups: The Emu oil group received topical Emu oil twice daily, whereas the control was left untreated. Skin biopsies were obtained on days 4, 7, 10, and 14 of the experiment. Then the specimens were viewed with Olympus SZX research microscope. The Emu oil treated burns were found to heal more slowly and inflammation lasted longer in this group. The number of hair follicles in the margins of the wounds increased through time in the Emu oil group compared to the control group. Also, the hair follicles in the Emu oil group were in several layers and seemed to be more active and mature. Moreover, Emu oil had a positive effect on fibrogenesis and synthesis of collagen. The findings indicate that although Emu oil delays the healing process, it has a positive effect on wound healing and it increases the number of hair follicles in the margins of the wound. PMID:27069472

Carcinogenicity assessment of the Hedgehog pathway inhibitor, vismodegib in Tg.rasH2 mice and Sprague-Dawley rats.

PubMed

Li, Jinze; Morinello, Eric; Larsen, Thomas; Frost, Denzil; Caro, Ivor; Gould, Stephen; Wong, Lisa; Hendricks, Angela; Dybdal, Noel; Dambach, Donna; Schutten, Melissa

2018-02-01

Vismodegib (also known as GDC-0449) is a novel small molecule inhibitor of the Hedgehog (Hh) signaling pathway currently approved for the treatment of metastatic or locally advanced basal cell carcinoma (BCC) in humans. Its tumorigenic potential was assessed in dedicated carcinogenicity studies in rasH2 transgenic (Tg.rasH2) mice and Sprague Dawley (SD) rats. Tumorigenicity potential of vismodegib was identified in rats only and was limited to benign hair follicle tumors, including pilomatricomas and keratoacanthomas at exposures of ≥0.1-fold and ≥0.6-fold, respectively, of the steady-state exposure (AUC 0-24h ) of the recommended human dose. No malignant tumors were identified in either species. Overall, the totality of pharmacology and nonclinical safety data (lack of genotoxicity, in vitro secondary pharmacological binding, and immunoregulatory effects, and limited effects on the endocrine system) suggests that the development of the benign hair follicle tumors may be related to pharmacologically-mediated disruption of hair follicle morphogenesis, although the exact mechanism of tumorigenesis is unclear. Hair follicle tumors have not been reported in vismodegib-treated patients. The relevance of this finding in rats to patients is uncertain. Copyright © 2018 Elsevier Inc. All rights reserved.

Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

PubMed Central

Wang, Xiaojie; Hao, Jianqiang; Leung, Gigi; Breitkopf, Trisia; Wang, Eddy; Kwong, Nicole; Akhoundsadegh, Noushin; Warnock, Garth L.; Shapiro, Jerry; McElwee, Kevin J.

2015-01-01

Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation. PMID:26000314

Apoptosis of hair follicle cells in the second-degree burn wound unders hypernatremic conditions.

PubMed

Harada, T; Izaki, S; Tsutsumi, H; Kobayashi, M; Kitamura, K

1998-08-01

Progressive burn wound necrosis is an important factor as a cause of delayed healing during clinical therapy of burns. Among the causes of progressive necrosis have been attributed an insufficient blood supply or a dehydration at the zone of stasis just beneath the zone of coagulation. In a previous study evidence was presented that hypernatremia, an osmotic injury, may act to promote progressive tissue or cell death of the superficial dermal wound resulting from a heat injury. To test this hypothesis pathological features of cell death in the second-degree burn wound in the rat with hypernatremia were investigated and evidence for apoptosis in hair follicle cells was observed. Rats in the hypernatremic group were administered 10 ml of hypertonic sodium solution (850 meq 1(-1)) and the control rats were treated with 10 ml of hyponatremic solution (100 meq 1(-1)) to prevent hypernatremia. After 24 h postburn the average incidence of hair follicles (ratio to the normal skin) in the hypernatremic group was 30.1 +/-11.6 per cent and significantly lower when compared with the control group (87.6+/-6.0 per cent). The numbers of hair follicles were studied by haematoxylin and eosin stain, and the apoptotic process was investigated by an immunochemical assay and electron microscopy.

Variability of hair coat and skin traits as related to adaptation in Criollo Limonero cattle.

PubMed

Landaeta-Hernández, Antonio; Zambrano-Nava, Sunny; Hernández-Fonseca, Juan P; Godoy, Rosario; Calles, Marcos; Iragorri, José L; Añez, Lauderys; Polanco, Miguel; Montero-Urdaneta, Merilio; Olson, Tim

2011-03-01

The variation in hair coat and skin histology traits of Criollo Limonero cattle was analyzed using 213 Criollo Limonero females. Skin biopsies were obtained from slick-haired (N=16) and normal-haired (N=14) animals. Measured traits included hair length (HL), color coat (CC), number of hair follicles per square centimeter (NHF), sweat glands per square centimeter (NSG), sweat glands size (SGS), sebaceous glands per square centimeter (NSBG), blood vessels per square centimeter (NBV), and thickness of epidermis (TE). Hair length differed (P<0.001) between slick- and normal-haired animals (4.9 ± 0.12 vs 10.9 ± 0.20, respectively). Differences (P<0.01) in CC (Bayo = 144/67.6% vs Red = 69/32.4%) and HL (slick-haired = 199/93.4% vs normal-haired = 14/6.5%) were found. Distribution of slick- and normal-haired animals differed (P<0.01) between bayo-coated and red-coated (139/62.2% vs 9/4.2%; respectively). Most (P<0.05) red-coated animals belonged to a single family. No differences (P>0.05) were found between slick-haired and normal-haired animals in NHF (637 ± 164 vs 587 ± 144, respectively), NSG (556 ± 134 vs 481 ± 118, respectively), NSBG (408 ± 87 vs 366 ± 77, respectively), NBV (1628 ± 393 vs 1541 ± 346, respectively), and TE (1.24 ± 0.14 vs 1.32 ± 0.12, respectively). However, SGS was greater (P<0.01) in slick-haired than normal-haired animals. In conclusion, Criollo Limonero cattle are predominantly bayo-coated, slick-haired, with a reduced number of hair follicles relative to Zebu cattle, sweat and sebaceous glands in proportion to hair follicle numbers, and with a high blood flow irrigating the skin. There is a sub-group of red-coated animals with yellow or cream skin, thicker epidermis, and with a higher frequency of normal-haired animals. It appears that the slick hair gene has been favored by natural selection in this breed.

Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X.

PubMed

Brunner, Magdalena A T; Jagannathan, Vidhya; Waluk, Dominik P; Roosje, Petra; Linek, Monika; Panakova, Lucia; Leeb, Tosso; Wiener, Dominique J; Welle, Monika M

2017-01-01

Alopecia X is a hair cycle arrest disorder in Pomeranians. Histologically, kenogen and telogen hair follicles predominate, whereas anagen follicles are sparse. The induction of anagen relies on the activation of hair follicle stem cells and their subsequent proliferation and differentiation. Stem cell function depends on finely tuned interactions of signaling molecules and transcription factors, which are not well defined in dogs. We performed transcriptome profiling on skin biopsies to analyze altered molecular pathways in alopecia X. Biopsies from five affected and four non-affected Pomeranians were investigated. Differential gene expression revealed a downregulation of key regulator genes of the Wnt (CTNNB1, LEF1, TCF3, WNT10B) and Shh (SHH, GLI1, SMO, PTCH2) pathways. In mice it has been shown that Wnt and Shh signaling results in stem cell activation and differentiation Thus our findings are in line with the lack of anagen hair follicles in dogs with Alopecia X. We also observed a significant downregulation of the stem cell markers SOX9, LHX2, LGR5, TCF7L1 and GLI1 whereas NFATc1, a quiescence marker, was upregulated in alopecia X. Moreover, genes coding for enzymes directly involved in the sex hormone metabolism (CYP1A1, CYP1B1, HSD17B14) were differentially regulated in alopecia X. These findings are in agreement with the so far proposed but not yet proven deregulation of the sex hormone metabolism in this disease.

PW1 gene/paternally expressed gene 3 (PW1/Peg3) identifies multiple adult stem and progenitor cell populations

PubMed Central

Besson, Vanessa; Smeriglio, Piera; Wegener, Amélie; Relaix, Frédéric; Nait Oumesmar, Brahim; Sassoon, David A.; Marazzi, Giovanna

2011-01-01

A variety of markers are invaluable for identifying and purifying stem/progenitor cells. Here we report the generation of a murine reporter line driven by Pw1 that reveals cycling and quiescent progenitor/stem cells in all adult tissues thus far examined, including the intestine, blood, testis, central nervous system, bone, skeletal muscle, and skin. Neurospheres generated from the adult PW1-reporter mouse show near 100% reporter-gene expression following a single passage. Furthermore, epidermal stem cells can be purified solely on the basis of reporter-gene expression. These cells are clonogenic, repopulate the epidermal stem-cell niches, and give rise to new hair follicles. Finally, we demonstrate that only PW1 reporter-expressing epidermal cells give rise to follicles that are capable of self-renewal following injury. Our data demonstrate that PW1 serves as an invaluable marker for competent self-renewing stem cells in a wide array of adult tissues, and the PW1-reporter mouse serves as a tool for rapid stem cell isolation and characterization. PMID:21709251

Chemotherapy-induced alopecia in mice. Induction by cyclophosphamide, inhibition by cyclosporine A, and modulation by dexamethasone.

PubMed Central

Paus, R.; Handjiski, B.; Eichmüller, S.; Czarnetzki, B. M.

1994-01-01

We introduce cyclophosphamide-induced alopecia (CYP-IA) in C57BL-6 mice as a clinically relevant model for studying the biology of chemotherapy-induced alopecia and for developing anti-alopecia drugs. One injection of CYP to mice with all back skin follicles in anagen VI induces severe alopecia that strikingly reproduces the follicle response, recovery, and histopathology seen in human CYP-IA. CYP dose-dependently induces abnormal follicular melanogenesis and dystrophic anagen or, in more severely damaged follicles, dystrophic catagen. Both dystrophy forms are followed by an extremely shortened telogen phase, but differ in the associated hair loss and in recovery patterns, which determines hair regrowth. This follicular response to CYP can be manipulated pharmacologically: systemic cyclosporine A shifts it toward a mild form of dystrophic anagen, thus retarding CYP-IA and prolonging "primary recovery". Topical dexamethasone, in contrast, forces follicles into dystrophic catagen, which augments CYP-IA, but accelerates the regrowth of normally pigmented hair ("secondary recovery"). Images Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 Figure 8 Figure 10 PMID:8160773

Watching stem cells at work with a flexible multiphoton tomograph

NASA Astrophysics Data System (ADS)

Uchugonova, Aisada; Hoffmann, Robert; Weinigel, Martin; König, Karsten

2012-03-01

There is a high demand for non-invasive imaging techniques that allow observation of stem cells in their native environment without significant input on cell metabolism, reproduction, and behavior. Easy accessible hair follicle pluripotent stem cells in the bulge area and dermal papilla are potential sources for stem cell based therapy. It has been shown that these cells are able to generate hair, non-follicle skin cells, nerves, vessels, smooth muscles etc. and may participate in wound healing processes. We report on the finding of nestin-GFP expressing stem cells in their native niche in the bulge of the hair follicle of living mice by using high-resolution in-vivo multiphoton tomography. The 3D imaging with submicron resolution was based on two-photon induced fluorescence and second harmonic generation (SHG) of collagen. Migrating stem cells from the bulge to their microenvironment have been detected inside the skin during optical deep tissue sectioning.

Large-bodied Demodex mite infestation in 4 dogs.

PubMed

Hillier, Andrew; Desch, Clifford E

2002-03-01

Large-bodied Demodex mites were detected in 4 dogs. The mites were readily detected in material obtained via deep skin scrapings and were most commonly found on the trunk. The mites were distinguishable from D. canis, because adult males were approximately 100% longer and adult females were approximately 50% longer than adult male and female D. canis mites, respectively. The large-bodied mites were found in the hair follicles, sebaceous ducts, and sebaceous glands in histologic sections of skin from 2 dogs. All dogs had adult-onset generalized demodicosis. Two dogs had coexistent iatrogenic hypercortisolism, 1 dog had hypothyroidism, and 1 dog did not have coexistent disease. Infestations responded to miticidal therapy, control of the coexistent disease, or both.

Human epithelial hair follicle stem cells and their progeny: current state of knowledge, the widening gap in translational research and future challenges.

PubMed

Purba, Talveen S; Haslam, Iain S; Poblet, Enrique; Jiménez, Francisco; Gandarillas, Alberto; Izeta, Ander; Paus, Ralf

2014-05-01

Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain and renew the continuously cycling hair follicle (HF), supply cells that produce the keratinized hair shaft and aid in the reepithelialization of injured skin. Therefore, their study is biologically and clinically important, from alopecia to carcinogenesis and regenerative medicine. However, human eHFSCs remain ill defined compared to their murine counterparts, and it is unclear which murine eHFSC markers really apply to the human HF. We address this by reviewing current concepts on human eHFSC biology, their immediate progeny and their molecular markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber-EP4. After delineating how human eHFSCs may be selectively targeted experimentally, we close by defining as yet unmet key challenges in human eHFSC research. The ultimate goal is to transfer emerging concepts from murine epithelial stem cell biology to human HF physiology and pathology. © 2014 WILEY Periodicals, Inc.

An Integrated Analysis of MicroRNA and mRNA Expression Profiles to Identify RNA Expression Signatures in Lambskin Hair Follicles in Hu Sheep

PubMed Central

Lv, Xiaoyang; Sun, Wei; Yin, Jinfeng; Ni, Rong; Su, Rui; Wang, Qingzeng; Gao, Wen; Bao, Jianjun; Yu, Jiarui; Wang, Lihong; Chen, Ling

2016-01-01

Wave patterns in lambskin hair follicles are an important factor determining the quality of sheep’s wool. Hair follicles in lambskin from Hu sheep, a breed unique to China, have 3 types of waves, designated as large, medium, and small. The quality of wool from small wave follicles is excellent, while the quality of large waves is considered poor. Because no molecular and biological studies on hair follicles of these sheep have been conducted to date, the molecular mechanisms underlying the formation of different wave patterns is currently unknown. The aim of this article was to screen the candidate microRNAs (miRNA) and genes for the development of hair follicles in Hu sheep. Two-day-old Hu lambs were selected from full-sib individuals that showed large, medium, and small waves. Integrated analysis of microRNA and mRNA expression profiles employed high-throughout sequencing technology. Approximately 13, 24, and 18 differentially expressed miRNAs were found between small and large waves, small and medium waves, and medium and large waves, respectively. A total of 54, 190, and 81 differentially expressed genes were found between small and large waves, small and medium waves, and medium and large waves, respectively, by RNA sequencing (RNA-seq) analysis. Differentially expressed genes were classified using gene ontology and pathway analyses. They were found to be mainly involved in cell differentiation, proliferation, apoptosis, growth, immune response, and ion transport, and were associated with MAPK and the Notch signaling pathway. Reverse transcription-polymerase chain reaction (RT-PCR) analyses of differentially-expressed miRNA and genes were consistent with sequencing results. Integrated analysis of miRNA and mRNA expression indicated that, compared to small waves, large waves included 4 downregulated miRNAs that had regulatory effects on 8 upregulated genes and 3 upregulated miRNAs, which in turn influenced 13 downregulated genes. Compared to small waves, medium waves included 13 downregulated miRNAs that had regulatory effects on 64 upregulated genes and 4 upregulated miRNAs, which in turn had regulatory effects on 22 downregulated genes. Compared to medium waves, large waves consisted of 13 upregulated miRNAs that had regulatory effects on 48 downregulated genes. These differentially expressed miRNAs and genes may play a significant role in forming different patterns, and provide evidence for the molecular mechanisms underlying the formation of hair follicles of varying patterns. PMID:27404636

A guide to studying human hair follicle cycling in vivo

PubMed Central

Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A.; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan

2015-01-01

Hair follicles (HFs) undergo life-long cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative “quiescence” (telogen). Since HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. While available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. Here, we present such a guide, which uses objective, well-defined, and reproducible criteria and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in sub-optimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. PMID:26763421

Hematological and hepatic effects of vascular epidermal growth factor (VEGF) used to stimulate hair growth in an animal model.

PubMed

Gnann, Laís Angelo; Castro, Rafael Ferreira; Azzalis, Ligia Ajaime; Feder, David; Perazzo, Fabio Ferreira; Pereira, Edimar Cristiano; Rosa, Paulo César Pires; Junqueira, Virginia Berlanga Campos; Rocha, Katya Cristina; Machado, Carlos D' Aparecida; Paschoal, Francisco Camargo; de Abreu, Luiz Carlos; Valenti, Vitor Engrácia; Fonseca, Fernando Luiz Affonso

2013-10-29

Alopecia areata is the hair loss usually reversible, in sharply defined areas. The treatment of alopecia using growth factors shows interesting activity in promoting hair growth. In this concept, VEGF (vascular endothelial growth factor) is a marker of angiogenesis, stimulating hair growth by facilitating the supply of nutrients to the hair follicle, increasing follicular diameter. The aim of this study was the evaluation of a topical gel enriched with VEGF liposomes on the hair growth stimulation and its toxicological aspects. Mesocricetus auratus were randomly divided into three groups. Control group was treated with Aristoflex® gel, 1% group with the same gel but added 1% VEGF and 3% group with 3% VEGF. Biochemical, hematological and histological analyses were done. At the end of the experiment (15th day of VEGF treatment) efficacy was determined macroscopically by hair density dermatoscopy analysis, and microscopically by hair diameter analysis. They both demonstrated that hair of the VEGF group increased faster and thicker than control. On the other hand, biochemical and hematological results had shown that VEGF was not 100% inert. VEGF increased hair follicle area, but more studies are necessary to confirm its toxicity.

Tufted folliculitis. A specific bacterial disease?

PubMed

Dalziel, K L; Telfer, N R; Wilson, C L; Dawber, R P

1990-02-01

Residual groups of hair follicles and unusual "tufts" of multiple hairs emerging from single follicular openings have been described in scarring alopecia associated with staphylococcal infection. Various mechanisms have been proposed to explain these findings. Histological study of four cases suggests that retention of telogen hairs through several hair cycles may be responsible for this phenomenon.

Jet fuel toxicity: skin damage measured by 900-MHz MRI skin microscopy and visualization by 3D MR image processing.

PubMed

Sharma, Rakesh; Locke, Bruce R

2010-09-01

The toxicity of jet fuels was measured using noninvasive magnetic resonance microimaging (MRM) at 900-MHz magnetic field. The hypothesis was that MRM can visualize and measure the epidermis exfoliation and hair follicle size of rat skin tissue due to toxic skin irritation after skin exposure to jet fuels. High-resolution 900-MHz MRM was used to measure the change in size of hair follicle, epidermis thickening and dermis in the skin after jet fuel exposure. A number of imaging techniques utilized included magnetization transfer contrast (MTC), spin-lattice relaxation constant (T1-weighting), combination of T2-weighting with magnetic field inhomogeneity (T2*-weighting), magnetization transfer weighting, diffusion tensor weighting and chemical shift weighting. These techniques were used to obtain 2D slices and 3D multislice-multiecho images with high-contrast resolution and high magnetic resonance signal with better skin details. The segmented color-coded feature spaces after image processing of the epidermis and hair follicle structures were used to compare the toxic exposure to tetradecane, dodecane, hexadecane and JP-8 jet fuels. Jet fuel exposure caused skin damage (erythema) at high temperature in addition to chemical intoxication. Erythema scores of the skin were distinct for jet fuels. The multicontrast enhancement at optimized TE and TR parameters generated high MRM signal of different skin structures. The multiple contrast approach made visible details of skin structures by combining specific information achieved from each of the microimaging techniques. At short echo time, MRM images and digitized histological sections confirmed exfoliated epidermis, dermis thickening and hair follicle atrophy after exposure to jet fuels. MRM data showed correlation with the histopathology data for epidermis thickness (R(2)=0.9052, P<.0002) and hair root area (R(2)=0.88, P<.0002). The toxicity of jet fuels on skin structures was in the order of tetradecane>hexadecane>dodecane. The method showed a sensitivity of 87.5% and a specificity of 75%. By MR image processing, different color-coded skin structures were extracted and 3D shapes of the epidermis and hair follicle size were compared. In conclusion, high-resolution MRM measured the change in skin epidermis and hair follicle size due to toxicity of jet fuels. MRM offers a three-dimensional spatial visualization of the change in skin structures as a method of toxicity evaluation and for comparison of jet fuels.

STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction.

PubMed

Legrand, Julien M D; Roy, Edwige; Ellis, Jonathan J; Francois, Mathias; Brooks, Andrew J; Khosrotehrani, Kiarash

2016-09-01

Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen), and rest (telogen) regulated by their mesenchymal component, the dermal papilla (DP). On the basis of the reports of its specific expression in the DP, we investigated signal transducer and activator of transcription (STAT5) activation during hair development and cycling. STAT5 activation in the DP began in late catagen, reaching a peak in early anagen before disappearing for the rest of the cycle. This was confirmed by the expression profile of suppressor of cytokine signaling 2, a STAT5 target in the DP. This pattern of expression starts after the first postnatal hair cycle. Quantification of hair cycling using the Flash canonical Wnt signaling in vivo bioluminescence reporter found that conditional knockout of STAT5A/B in the DP targeted through Cre-recombinase under the control of the Sox18 promoter resulted in delayed anagen entry compared with control. Microarray analysis of STAT5 deletion versus control revealed key changes in tumor necrosis factor-α, Wnt, and fibroblast growth factor ligands, known for their role in inducing anagen entry. We conclude that STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Hair growth promoting activity of discarded biocomposite keratin extract.

PubMed

Akanda, Md Rashedunnabi; Kim, Hak-Yong; Park, Mira; Kim, In-Shik; Ahn, Dongchoon; Tae, Hyun-Jin; Park, Byung-Yong

2017-08-01

Keratin biomaterial has been used in regenerative medicine owing to its in-vivo and in-vitro biocompatibility. The present study was aimed to investigate the hair growth promoting activity of keratin extract and its mechanism of action. Keratin extract was topically applied on the synchronized depilated dorsal skin of telogenic C57BL/6 mice and promoted hair growth by inducing the anagen phase. The histomorphometric observation indicated significantly increases the number, shaft of hair follicles and deep subcutis area in the keratin extract treated group in contrast to the control group, which was considered an indication of anagen phase induction. Subsequently, the quantitative real-time polymerase chain reaction analysis revealed that fibroblast growth factor-10, vascular endothelial growth factor, insulin-like growth factor-1, β-catenin, and Shh were expressed earlier in the keratin extract-treated group than in the control group. Besides, keratin extract has been observed to be biocompatible when analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 4',6-diamidino-2-phenylindole staining using immortalized human keratinocyte cells, showing more than 90% cell viability. Our study demonstrated that keratin extract stimulating hair follicle growth by inducing the growth phase; anagen in telogenic C57BL/6 mice and thus the topical application of keratin extract may represent a promising biomaterial for the management and applications of hair follicle disorder.

Alterations in Hair Follicle Dynamics in Women

PubMed Central

Piérard-Franchimont, Claudine; Piérard, Gérald E.

2013-01-01

Endocrine changes supervening after parturition and menopause participate in the control of sebum production and hair growth modulation. The ensuing conditions include some peculiar aspects of hair loss (effluvium), alopecia, and facial hirsutism. The hair cycling is of major clinical relevance because most hair growth disorders result from disturbances in this chronobiological feature. Of note, any correlation between a biologic abnormality and hair cycling disturbance does not prove a relationship of causality. The proportion of postmenopausal women is rising in the overall population. Therefore, the prevalence of these hair follicle disturbances is globally on the rise. Current therapies aim at correcting the underlying hormonal imbalances, and at improving the overall cosmetic appearance. However, in absence of pathogenic diagnosis and causality criteria, chances are low that a treatment given by the whims of fate will adequately control hair effluvium. The risk and frequency of therapeutic inertia are further increased. When the hair loss is not controlled and/or compensated by growth of new hairs, several clinical aspects of alopecia inexorably develop. Currently, there is little evidence supporting any specific treatment for these endocrine hair disorders in post-partum and postmenopausal women. Current hair treatment strategies are symptomatic and nonspecific so current researchers aim at developing new, targeted methods. PMID:24455742

Folliculitis

MedlinePlus

... in the groin area. This condition may leave dark raised scars (keloids). Pityrosporum (pit-ih-ROS-puh- ... furunculosis) Permanent skin damage, such as scarring or dark spots Destruction of hair follicles and permanent hair ...

The effect of cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, on human hair growth with the dual promoting mechanisms.

PubMed

Choi, Hye-In; Kim, Dong Young; Choi, Soon-Jin; Shin, Chang-Yup; Hwang, Sungjoo Tommy; Kim, Kyu Han; Kwon, Ohsang

2018-07-01

Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, increases the intracellular level of cyclic adenosine monophosphate to cause vasodilation. Topical application of cilostazol is reported to improve local blood flow and enhance wound healing; however, its effect on human hair follicles is unknown. The purpose of this study was to determine the effect of cilostazol on hair growth. We investigated the expression of PDE3 in human dermal papilla cells (DPCs), outer root sheath cells (ORSCs), and hair follicles. The effects of cilostazol on DPC and ORSC proliferation were evaluated using BrdU and WST-1 assays. The expression of various growth factors in DPCs was investigated by growth factor antibody array. Additionally, hair shaft elongation was measured using ex vivo hair follicle organ cultures, and anagen induction was evaluated in C57BL/6 mice. Finally, the effects of cilostazol on vessel formation and activation of the mitogen-activated protein kinase pathway were evaluated. We confirmed high mRNA and protein expression of PDE3 in human DPCs. Cilostazol not only enhanced the proliferation of human DPCs but also regulated the secretion of several growth factors responsible for hair growth. Furthermore, it promoted hair shaft elongation ex vivo, with increased proliferation of matrix keratinocytes. Cilostazol also accelerated anagen induction by stimulating vessel formation and upregulating the levels of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase, and P38 after its topical application in C57BL/6 mice. Our results show that cilostazol promotes hair growth and may serve as a therapeutic agent for the treatment of alopecia. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Lactate dehydrogenase activity drives hair follicle stem cell activation

PubMed Central

Aimee, Flores; John, Schell; Abby, Krall; David, Jelinek; Matilde, Miranda; Melina, Grigorian; Daniel, Braas; White Andrew, C; Jessica, Zhou; Nick, Graham; Thomas, Graeber; Pankaj, Seth; Denis, Evseenko; Hilary, Coller; Jared, Rutter; Heather, Christofk; Lowry William, E

2017-01-01

Summary While normally dormant, Hair Follicle Stem Cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allow them to remain dormant and yet quickly respond to appropriate proliferative stimuli. PMID:28812580

A Novel Mechanism for the Pathogenesis of Nonmelanoma Skin Cancer Resulting from Early Exposure to Ultraviolet Light

DTIC Science & Technology

2013-09-01

entering the circulation, and traveling throughout the body may be a new behavior of epidermal stem cells. We proposed that sunburn following...response to sunburn . We address the following question: Do hair follicle stem cells migrate from the skin following sunburn as a consequence of ultraviolet...light induced inflammation? Our hypothesis is that sunburn makes the hair follicles stem cells leave the skin and enter the blood circulation, and

Exposure to non-ionizing electromagnetic fields emitted from mobile phones induced DNA damage in human ear canal hair follicle cells.

PubMed

Akdag, Mehmet; Dasdag, Suleyman; Canturk, Fazile; Akdag, Mehmet Zulkuf

2018-01-01

The aim of this study was to investigate effect of radiofrequency radiation (RFR) emitted from mobile phones on DNA damage in follicle cells of hair in the ear canal. The study was carried out on 56 men (age range: 30-60 years old)in four treatment groups with n = 14 in each group. The groups were defined as follows: people who did not use a mobile phone (Control), people use mobile phones for 0-30 min/day (second group), people use mobile phones for 30-60 min/day (third group) and people use mobile phones for more than 60 min/day (fourth group). Ear canal hair follicle cells taken from the subjects were analyzed by the Comet Assay to determine DNA damages. The Comet Assay parameters measured were head length, tail length, comet length, percentage of head DNA, tail DNA percentage, tail moment, and Olive tail moment. Results of the study showed that DNA damage indicators were higher in the RFR exposure groups than in the control subjects. In addition, DNA damage increased with the daily duration of exposure. In conclusion, RFR emitted from mobile phones has a potential to produce DNA damage in follicle cells of hair in the ear canal. Therefore, mobile phone users have to pay more attention when using wireless phones.

Folliculitis in prurigo pigmentosa: a proposed pathogenesis based on clinical and pathological observation.

PubMed

Kafle, Santosh U; Swe, Sai Myint; Hsiao, Pa-Fan; Tsai, Yi-Chiun; Wu, Yu-Hung

2017-01-01

Prurigo pigmentosa is a rare inflammatory dermatosis whose exact etiology is not understood yet. The purpose of this study was to provide evidence of hair follicle involvement in the pathogenesis by analyzing its clinicopathologic features. Patients who fulfilled both the clinical and histological diagnostic criteria of prurigo pigmentosa were recruited. Their histopathologic findings, clinical features and medical histories were analyzed. A total of 32 confirmed patients were enrolled from 2002 to 2013. Their ages ranged from 11 to 79 years with a female predominance. Patient lesions were primarily reddish-brown and located on the back. A total of 25 patients (78%) had pathological involvement of hair follicles, either bacterial colonies in the hair follicles (21/32, 66%), folliculitis (8/32, 25%) or perifolliculitis (15/32, 47%). There was a significantly higher proportion of patients with hair follicle involvement compared with control groups with either noninflammatory (5/43, 12%, p < 0.001) or inflammatory skin diseases (12/32, 38%, p = 0.002) on the back. Minocycline was an effective antibiotic treatment either singly or in combination with steroids. The frequent presence of bacterial colonies along with sequelae of inflammatory changes on biopsy provides new evidence to support the theory that prurigo pigmentosa is a reactive inflammation associated with bacterial folliculitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Skin physiology in microgravity: a 3-month stay aboard ISS induces dermal atrophy and affects cutaneous muscle and hair follicles cycling in mice.

PubMed

Neutelings, Thibaut; Nusgens, Betty V; Liu, Yi; Tavella, Sara; Ruggiu, Alessandra; Cancedda, Ranieri; Gabriel, Maude; Colige, Alain; Lambert, Charles

2015-01-01

The Mice Drawer System (MDS) Tissue Sharing program was the longest rodent space mission ever performed. It provided 20 research teams with organs and tissues collected from mice having spent 3 months on the International Space Station (ISS). Our participation to this experiment aimed at investigating the impact of such prolonged exposure to extreme space conditions on mouse skin physiology. Mice were maintained in the MDS for 91 days aboard ISS (space group (S)). Skin specimens were collected shortly after landing for morphometric, biochemical, and transcriptomic analyses. An exact replicate of the experiment in the MDS was performed on ground (ground group (G)). A significant reduction of dermal thickness (-15%, P =0.05) was observed in S mice accompanied by an increased newly synthetized procollagen (+42%, P =0.03), likely reflecting an increased collagen turnover. Transcriptomic data suggested that the dermal atrophy might be related to an early degradation of defective newly formed procollagen molecules. Interestingly, numerous hair follicles in growing anagen phase were observed in the three S mice, validated by a high expression of specific hair follicles genes, while only one mouse in the G controls showed growing hairs. By microarray analysis of whole thickness skin, we observed a significant modulation of 434 genes in S versus G mice. A large proportion of the upregulated transcripts encoded proteins related to striated muscle homeostasis. These data suggest that a prolonged exposure to space conditions may induce skin atrophy, deregulate hair follicle cycle, and markedly affect the transcriptomic repertoire of the cutaneous striated muscle panniculus carnosus.

A Microarray-Based Analysis Reveals that a Short Photoperiod Promotes Hair Growth in the Arbas Cashmere Goat.

PubMed

Liu, Bin; Gao, Fengqin; Guo, Jun; Wu, Dubala; Hao, Bayasihuliang; Li, Yurong; Zhao, Cunfa

2016-01-01

Many animals exhibit different behaviors in different seasons. The photoperiod can have effects on migration, breeding, fur growth, and other processes. The cyclic growth of the fur and feathers of some species of mammals and birds, respectively, is stimulated by the photoperiod as a result of hormone-dependent regulation of the nervous system. To further examine this phenomenon, we evaluated the Arbas Cashmere goat (Capra hircus), a species that is often used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclic cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Assessments of tissue sections indicated that the short photoperiod significantly induced cashmere growth. This conclusion was supported by a comparison of the differences in gene expression between the short photoperiod and natural conditions using gene chip technology. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and these genes were found to be involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages. Knowledge about differences in the expression of these genes as well as their functions and periodic regulation patterns increases our understanding of Cashmere goat hair follicle growth. This study also provides preliminary data that may be useful for the development of an artificial method to improve cashmere production by controlling the light cycle, which has practical significance for livestock breeding.

Vitamin D Pathway Status and the Identification of Target Genes in the Mouse Mammary Gland

DTIC Science & Technology

2013-01-01

12 Palmer HG et al. The vitamin D receptor is a Wnt effector that controls hair follicle differentiation and specifies tumor type in adult epidermis...AD_________________ Award Number: W81XWH-11-1-0152 TITLE: Vitamin D pathway status and the...December 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0152 Vitamin D pathway status and the identification of target genes in the

A curated catalog of canine and equine keratin genes

PubMed Central

Pujar, Shashikant; McGarvey, Kelly M.; Welle, Monika; Galichet, Arnaud; Müller, Eliane J.; Pruitt, Kim D.; Leeb, Tosso

2017-01-01

Keratins represent a large protein family with essential structural and functional roles in epithelial cells of skin, hair follicles, and other organs. During evolution the genes encoding keratins have undergone multiple rounds of duplication and humans have two clusters with a total of 55 functional keratin genes in their genomes. Due to the high similarity between different keratin paralogs and species-specific differences in gene content, the currently available keratin gene annotation in species with draft genome assemblies such as dog and horse is still imperfect. We compared the National Center for Biotechnology Information (NCBI) (dog annotation release 103, horse annotation release 101) and Ensembl (release 87) gene predictions for the canine and equine keratin gene clusters to RNA-seq data that were generated from adult skin of five dogs and two horses and from adult hair follicle tissue of one dog. Taking into consideration the knowledge on the conserved exon/intron structure of keratin genes, we annotated 61 putatively functional keratin genes in both the dog and horse, respectively. Subsequently, curators in the RefSeq group at NCBI reviewed their annotation of keratin genes in the dog and horse genomes (Annotation Release 104 and Annotation Release 102, respectively) and updated annotation and gene nomenclature of several keratin genes. The updates are now available in the NCBI Gene database (https://www.ncbi.nlm.nih.gov/gene). PMID:28846680

Organ-level quorum sensing directs regeneration in hair stem cell populations

PubMed Central

Chen, Chih-Chiang; Wang, Lei; Plikus, Maksim V.; Jiang, Ting Xin; Murray, Philip J.; Ramos, Raul; Guerrero-Juarez, Christian F.; Hughes, Michael W; Lee, Oscar K.; Shi, Songtao; Widelitz, Randall B.; Lander, Arthur D.; Chuong, Cheng Ming

2015-01-01

SUMMARY Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair removal, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Removing hair at different densities leads to a regeneration of up to 5 times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells. PMID:25860610

Hair growth-promoting effect of Carthamus tinctorius floret extract.

PubMed

Junlatat, Jintana; Sripanidkulchai, Bungorn

2014-07-01

The florets of Carthamus tinctorius L. have traditionally been used for hair growth promotion. This study aimed to examine the potential of hydroxysafflor yellow A-rich C. tinctorius extract (CTE) on hair growth both in vitro and in vivo. The effect of CTE on cell proliferation and hair growth-associated gene expression in dermal papilla cells and keratinocytes (HaCaT) was determined. In addition, hair follicles from mouse neonates were isolated and cultured in media supplemented with CTE. Moreover, CTE was applied topically on the hair-shaved skin of female C57BL/6 mice, and the histological profile of the skin was investigated. C. tinctorius floret ethanolic extract promoted the proliferation of both dermal papilla cells and HaCaT and significantly stimulated hair growth-promoting genes, including vascular endothelial growth factor and keratinocyte growth factor. In contrast, CTE suppressed the expression of transforming growth factor-β1 that is the hair loss-related gene. Furthermore, CTE treatment resulted in a significant increase in the length of cultured hair follicles and stimulated the growth of hair with local effects in mice. The results provided the preclinical data to support the potential use of CTE as a hair growth-promoting agent. Copyright © 2013 John Wiley & Sons, Ltd.

Expression of Notch pathway genes in mammalian epidermis and modulation by beta-catenin.

PubMed

Ambler, Carrie A; Watt, Fiona M

2007-06-01

The Notch pathway is required for hair follicle maintenance and is activated through beta-catenin induced transcription of the Notch ligand Jagged1. We show that hair follicles in the resting phase express low levels of Jagged1 and Hes1, and other Notch target genes are undetectable. In growing (anagen) follicles, Jagged1 and Hes1 expression increases, Hes5 and HeyL are expressed in distinct cell layers, and Hey2 is expressed in the dermal papilla. When beta-catenin is activated by means of an inducible transgene, Jagged1, Hes1, Hes5, HeyL, and Hey2 are up-regulated, the sites of expression being the same in beta-catenin induced ectopic follicles as in anagen follicles. beta-Catenin also induces Hey1 in dermal papilla cells. beta-Catenin-induced up-regulation of Jagged1 precedes induction of other Notch target genes. The different sites of expression of Hes and Hey genes suggest input from additional signaling pathways. Copyright 2007 Wiley-Liss, Inc.

[Hair and their environment].

PubMed

Piérard-Franchimont, C; Piérard, G E

2015-02-01

Hair is influenced by the effects of the daily environment. Some toxic xenobiotics slow down or block the cell renewal of the hair matrix, thus inhibiting hair growth. The ultraviolet light obviously influences the physical structure and physiology of the hair follicle. Tobacco is similarly responsible for negative influences on the evolution of various alopecias. Several cosmetic procedures for maintaining and making hair more attractive are not always harmless, and they occasionally represent a possible origin for alopecia.

Promotion of hair growth by newly synthesized ceramide mimetic compound.

PubMed

Park, Bu-Mahn; Bak, Soon-Sun; Shin, Kyung-Oh; Kim, Minhee; Kim, Daehwan; Jung, Sang-Hun; Jeong, Sekyoo; Sung, Young Kwan; Kim, Hyun Jung

2017-09-09

Based on the crucial roles of ceramides in skin barrier function, use of ceramides or their structural mimetic compounds, pseudoceramides, as cosmetic ingredients are getting more popular. While currently used pseudoceramides are intended to substitute the structural roles of ceramides in stratum corneum, development of bioactive pseudoceramides has been repeatedly reported. In this study, based on the potential involvement of sphingolipids in hair cycle regulation, we investigated the effects of newly synthesized pseudoceramide, bis-oleamido isopropyl alcohol (BOI), on hair growth using cultured human hair follicles and animal models. BOI treatment promoted hair growth in cultured human hair follicles ex vivo and induced earlier conversion of telogen into anagen. Although we did not find a significant enhancement of growth factor expression and follicular cell proliferation, BOI treatment resulted in an increased sphinganine and sphingosine contents as well as increased ceramides contents in cultured dermal papilla (DP) cells. Taken together, our data strongly suggest that biologically active pseudoceramide promotes hair growth by stimulating do novo synthesis of sphingolipids in DP cells. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of sebocytes cultured from nevus sebaceus on hair growth.

PubMed

Lee, Weon Ju; Cha, Hyun Wuk; Lim, Hyun Jung; Lee, Seok-Jong; Kim, Do Won

2012-10-01

Sebaceous glands are known to affect hair growth. Nevus sebaceus, a sebaceous gland hamartomas, presents as hairless patches. In this study, cultures of nevus sebaceus sebocytes (NSS) and normal scalp hair follicle sebocytes (NS) were used in performance of microarray, RT-PCR, western blot assay and immunofluorescence staining. NSS- and NS-conditioned media were also added to the culture of outer root sheath cells (ORSCs), dermal papilla cells (DPCs) or normal scalp hair follicle sebocytes. Results of this study showed a decrease in the survival rate of ORSCs and DPCs and hair growth in the NSS-conditioned medium-treated group, compared with the control and NS-conditioned medium-treated groups. An increase in expression of fibroblast growth factor (FGF)-5, Dickkopf-1 and inflammatory cytokines and a decrease in expression of Wnt10b and Lef1 were observed. In conclusion, NSS showed an increase in expression of hair growth-suppressing bioactive factors, including FGF-5, and a decrease in expression of hair growth-stimulating factors. © 2012 John Wiley & Sons A/S.

Observation of a system of linear loops formed by re-growing hairs on rat skin.

PubMed

Liu, Li-Yuan; Guo, Dong-Sheng; Xin, Xiu-Yu; Fang, Jin

2008-07-01

This paper details linear hair re-growth patterns observed in rats. Adult rats were shaved and observed. The first wave of hair re-growth did not distribute everywhere, but along specific craniocaudally-oriented lines. The hair-lines were 2-15 mm wide and ran from the head, through the torso to the limbs, and were symmetrical along the left and right sides of the body. The symmetric hair-lines from both sides of the body converged around the mouth, nose, and at the pubic region or ventral midline to form a system of hair-loop-lines (HLLs). The loops can be differentiated into four main patterns. The Dorsal Loop and the Lateral Dorsal Loop run along the dorsum and hindlimb. The Ventral Loop and Lateral Ventral Loop travel along the thorax, abdomen, and forelimb. These hair-lines coincide with our previously observed sympathetic-substance lines (SSLs) in the rat's skin. Histological observation indicates that rat hair follicles along the hair-lines were at anagen phase. The catecholamine histofluorescent check showed abundant sympathetic nerve fibers beneath the hair-lines. After the rats' hairs were dyed, and selected portions shaved, re-growth was only observed on the shaved portions, indicating that the linear hair growth closely correlated with the shaving. Lastly we examine the cause of the preferential re-growth and briefly discuss the purpose and physiological role of the HLL. (c) 2008 Wiley-Liss, Inc.

Protopanaxatirol type ginsenoside Re promotes cyclic growth of hair follicles via inhibiting transforming growth factor β signaling cascades.

PubMed

Li, Zheng; Ryu, Seung-Wook; Lee, Jungsul; Choi, Kyungsun; Kim, Sunchang; Choi, Chulhee

2016-02-19

Ginsenosides, the major bio-active ingredients included in Panax ginseng, have been known for the hair growth activity and used to treat patients who suffer from hair loss; however, the detailed mechanisms of this action are still largely unknown. This study was conducted to investigate the molecular and cellular mechanisms responsible for hair growth promoting effect of ginsenoside Re (GRe) in vitro and in vivo. Different doses of minoxidil and GRe were administered topically to the back regions of nude mice for up to 45 days, and hair shaft length and hair cycles were determined for hair promoting activities. Topical treatment of GRe significantly increased the hair shaft length and hair existent time, which was comparable to the action of minoxidil. We also demonstrated that GRe stimulated hair shaft elongation in the ex vivo cultures of vibrissa hair follicles isolated from C57BL/6 mouse. Systemic transcriptome analysis by next generation sequencing demonstrated that TGF-β-pathway related genes were selectively down-regulated by treatment of GRe in vivo, and the same treatment suppressed TGF-β-induced phosphorylation of ERK in HeLa cells. The results clearly indicated that GRe is the effective constituent in the ginseng on hair promotion via selective inhibition of the hair growth phase transition related signaling pathways, TGF-β signaling cascades. Copyright © 2016. Published by Elsevier Inc.

Strategy of topical vaccination with nanoparticles

NASA Astrophysics Data System (ADS)

Jung, Sascha; Patzelt, Alexa; Otberg, Nina; Thiede, Gisela; Sterry, Wolfram; Lademann, Juergen

2009-03-01

Liposomes in the nanosize range have been recognized as a versatile drug delivery system of both hydrophilic and lipophilic molecules. In order to develop a liposome-based topical vaccination strategy, five different types of liposomes were tested as a putative vaccine delivery system on pig ear skin. The investigated liposomes mainly varied in size, lipid composition, and surface charge. Using hydrophilic and hydrophobic fluorescent dyes as model drugs, penetration behavior was studied by means of confocal laser scanning microscopy of intact skin and histological sections, respectively. Follicular penetration of the liposomes was measured in comparison to a standard, nonliposomal formulation at different time points. Dependent on time but independent of their different characters, the liposomes showed a significantly higher penetration depth into the hair follicles compared to the standard formulation. The standard formulation reached a relative penetration depth of 30% of the full hair follicle length after seven days, whereas amphoteric and cationic liposomes had reached ~70%. Penetration depth of negatively charged liposomes did not exceed 50% of the total follicle length. The fluorescence dyes were mainly detected in the hair follicle; only a small amount of dye was found in the upper parts of the epidermis.

Strategy of topical vaccination with nanoparticles.

PubMed

Jung, Sascha; Patzelt, Alexa; Otberg, Nina; Thiede, Gisela; Sterry, Wolfram; Lademann, Juergen

2009-01-01

Liposomes in the nanosize range have been recognized as a versatile drug delivery system of both hydrophilic and lipophilic molecules. In order to develop a liposome-based topical vaccination strategy, five different types of liposomes were tested as a putative vaccine delivery system on pig ear skin. The investigated liposomes mainly varied in size, lipid composition, and surface charge. Using hydrophilic and hydrophobic fluorescent dyes as model drugs, penetration behavior was studied by means of confocal laser scanning microscopy of intact skin and histological sections, respectively. Follicular penetration of the liposomes was measured in comparison to a standard, nonliposomal formulation at different time points. Dependent on time but independent of their different characters, the liposomes showed a significantly higher penetration depth into the hair follicles compared to the standard formulation. The standard formulation reached a relative penetration depth of 30% of the full hair follicle length after seven days, whereas amphoteric and cationic liposomes had reached approximately 70%. Penetration depth of negatively charged liposomes did not exceed 50% of the total follicle length. The fluorescence dyes were mainly detected in the hair follicle; only a small amount of dye was found in the upper parts of the epidermis.

The inductive effect of ginsenoside F2 on hair growth by altering the WNT signal pathway in telogen mouse skin.

PubMed

Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Song, Hyun-Geun; Mavlonov, Gafurjon T; Yi, Tae-Hoo

2014-05-05

This study was conducted to confirm the possibility of using minor ginseng saponin F2 by oral administration on hair anagen induction effects. The signaling pathway and anagen induction effect of ginsenoside F2 were investigated and compared with finasteride on the effect of hair growth induction. The cell-based MTT assay results indicated that the proliferation rates of HHDPC and HaCaT treated with F2 significantly increased by 30% compared with the finasteride-treated group. A western blot study showed that the expression of β-catenin Lef-1 and DKK-1 increased by 140, 200% and decreased by 40% in the F2-treated group, respectively compared to that of finasteride-treated group. C57BL/6 mice were subjected to the same treatments. The hair growth promotion rates were compared with groups treated with finasteride, which was 20% higher in the F2-treated group. Tissue histological analysis results showed the number of hair follicles, thickness of the epidermis, and follicles of the anagen phase which increased in the F2-treated group, compared with the finasteride-treated groups. Moreover, the effect of F2 on hair growth was confirmed through the immunofluorescence (IF) methods indicating the expression aspect of Wnt signal pathway-related factors in the tissue of C57BL/6 mouse. Our results considered the expression increase in β-catenin, Lef-1 which was suggested as a major factor related to the development and growth of hair follicle and the decrease in DKK-1 when entering catagen by F2. As the data showed, F2 might be a potential new therapeutic source for anagen induction and hair growth through the Wnt signal pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

Module Based Complexity Formation: Periodic Patterning in Feathers and Hairs

PubMed Central

Chuong, Cheng-Ming; Yeh, Chao-Yuan; Jiang, Ting-Xin; Widelitz, Randall

2012-01-01

Patterns describe order which emerges from homogeneity. Complex patterns on the integument are striking because of their visibility throughout an organism's lifespan. Periodic patterning is an effective design because the ensemble of hair or feather follicles (modules) allows the generation of complexity, including regional variations and cyclic regeneration, giving the skin appendages a new lease on life. Spatial patterns include the arrangements of feathers and hairs in specified number, size, and spacing. We explore how a field of equivalent progenitor cells can generate periodically arranged modules based on genetic information, physical-chemical rules and developmental timing. Reconstitution experiments suggest a competitive equilibrium regulated by activators / inhibitors involving Turing reaction-diffusion. Temporal patterns result from oscillating stem cell activities within each module (micro-environment regulation), reflected as growth (anagen) and resting (telogen) phases during the cycling of feather and hair follicles. Stimulating modules with activators initiates the spread of regenerative hair waves, while global inhibitors outside each module (macro-environment) prevent this. Different wave patterns can be simulated by Cellular Automata principles. Hormonal status and seasonal changes can modulate appendage phenotypes, leading to “organ metamorphosis”, with multiple ectodermal organ phenotypes generated from the same precursors. We discuss potential evolutionary novel steps using this module based complexity in several amniote integument organs, exemplified by the spectacular peacock feather pattern. We thus explore the application of the acquired knowledge of patterning in tissue engineering. New hair follicles can be generated after wounding. Hairs and feathers can be reconstituted through self-organization of dissociated progenitor cells. PMID:23539312

Module-based complexity formation: periodic patterning in feathers and hairs.

PubMed

Chuong, Cheng-Ming; Yeh, Chao-Yuan; Jiang, Ting-Xin; Widelitz, Randall

2013-01-01

Patterns describe order which emerges from homogeneity. Complex patterns on the integument are striking because of their visibility throughout an organism’s lifespan. Periodic patterning is an effective design because the ensemble of hair or feather follicles (modules) allows the generation of complexity, including regional variations and cyclic regeneration, giving the skin appendages a new lease on life. Spatial patterns include the arrangements of feathers and hairs in specific number, size, and spacing.We explorehowa field of equivalent progenitor cells can generate periodically arranged modules based on genetic information, physical–chemical rules and developmental timing. Reconstitution experiments suggest a competitive equilibrium regulated by activators/inhibitors involving Turing reaction-diffusion. Temporal patterns result from oscillating stem cell activities within each module (microenvironment regulation), reflected as growth (anagen) and resting (telogen) phases during the cycling of feather and hair follicles. Stimulating modules with activators initiates the spread of regenerative hair waves, while global inhibitors outside each module (macroenvironment) prevent this. Different wave patterns can be simulated by cellular automata principles. Hormonal status and seasonal changes can modulate appendage phenotypes, leading to ‘organ metamorphosis’, with multiple ectodermal organ phenotypes generated from the same precursors. We discuss potential novel evolutionary steps using this module-based complexity in several amniote integument organs, exemplified by the spectacular peacock feather pattern. We thus explore the application of the acquired knowledge of patterning in tissue engineering. New hair follicles can be generated after wounding. Hairs and feathers can be reconstituted through self-organization of dissociated progenitor cells. © 2012 Wiley Periodicals, Inc.

Hematological and hepatic effects of vascular epidermal growth factor (VEGF) used to stimulate hair growth in an animal model

PubMed Central

2013-01-01

Background Alopecia areata is the hair loss usually reversible, in sharply defined areas. The treatment of alopecia using growth factors shows interesting activity in promoting hair growth. In this concept, VEGF (vascular endothelial growth factor) is a marker of angiogenesis, stimulating hair growth by facilitating the supply of nutrients to the hair follicle, increasing follicular diameter. The aim of this study was the evaluation of a topical gel enriched with VEGF liposomes on the hair growth stimulation and its toxicological aspects. Methods Mesocricetus auratus were randomly divided into three groups. Control group was treated with Aristoflex® gel, 1% group with the same gel but added 1% VEGF and 3% group with 3% VEGF. Biochemical, hematological and histological analyses were done. Results At the end of the experiment (15th day of VEGF treatment) efficacy was determined macroscopically by hair density dermatoscopy analysis, and microscopically by hair diameter analysis. They both demonstrated that hair of the VEGF group increased faster and thicker than control. On the other hand, biochemical and hematological results had shown that VEGF was not 100% inert. Conclusions VEGF increased hair follicle area, but more studies are necessary to confirm its toxicity. PMID:24168457

A Guide to Studying Human Hair Follicle Cycling In Vivo.

PubMed

Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan; Kim, Moonkyu; Paus, Ralf; Plikus, Maksim V

2016-01-01

Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Topical Treatment of Hair Loss with Formononetin by Modulating Apoptosis.

PubMed

Kim, Mi Hye; Choi, You Yeon; Lee, Ji Eun; Kim, Kyuseok; Yang, Woong Mo

2016-01-01

Formononetin is one of the main components of red clover plants and its role on hair regrowth against hair loss has not been established yet. In the present study, we assessed the potential effects of formononetin on alopecia, along with impaired hair cycles by induction of apoptosis-regression.Depilated C57BL/6 mice were used for monitoring the hair cycles. Formononetin (1 and 100 µM) was topically treated to the dorsal skin for 14 days. Topical formononetin treatment induced miniaturized hair follicles to recover to normal sizes. Tapering hair shaft began to grow newly, emerging from the hair follicles by formononetin. In addition, formononetin inhibited the activation of caspase-8 and decreased the procaspase-9 expression. As a result of formononetin treatment, anti-apoptotic Bcl-2 was up-regulated, whereas pro-apoptotic Bax and p53 were down-regulated, resulting in a decrease of caspase-3 activation. Formononetin showed the obvious inhibition of apoptosis under terminal deoxynucleotidyl transferase dUTP nick end labeling staining thereafter.Taken together, our findings demonstrate that formononetin exerted the hair regrowth effect on hair loss, in which the underlying mechanisms were associated with Fas/Fas L-induced caspase activation, thus inhibiting apoptosis. Georg Thieme Verlag KG Stuttgart · New York.

Low-Level Laser (Light) Therapy (LLLT) for Treatment of Hair Loss

PubMed Central

Avci, Pinar; Gupta, Gaurav K.; Clark, Jason; Wikonkal, Norbert; Hamblin, Michael R.

2013-01-01

Objective Alopecia is a common disorder affecting more than half of the population worldwide. Androgenetic alopecia, the most common type, affects 50% of males over the age of 40 and 75% of females over 65. Only two drugs have been approved so far (minoxidil and finasteride) and hair transplant is the other treatment alternative. This review surveys the evidence for low-level laser therapy (LLLT) applied to the scalp as a treatment for hair loss and discusses possible mechanisms of actions. Methods and Materials Searches of PubMed and Google Scholar were carried out using keywords alopecia, hair loss, LLLT, photobiomodulation. Results Studies have shown that LLLT stimulated hair growth in mice subjected to chemotherapy-induced alopecia and also in alopecia areata. Controlled clinical trials demonstrated that LLLT stimulated hair growth in both men and women. Among various mechanisms, the main mechanism is hypothesized to be stimulation of epidermal stem cells in the hair follicle bulge and shifting the follicles into anagen phase. Conclusion LLLT for hair growth in both men and women appears to be both safe and effective. The optimum wavelength, coherence and dosimetric parameters remain to be determined. PMID:23970445

Low-level laser (light) therapy (LLLT) for treatment of hair loss.

PubMed

Avci, Pinar; Gupta, Gaurav K; Clark, Jason; Wikonkal, Norbert; Hamblin, Michael R

2014-02-01

Alopecia is a common disorder affecting more than half of the population worldwide. Androgenetic alopecia, the most common type, affects 50% of males over the age of 40 and 75% of females over 65. Only two drugs have been approved so far (minoxidil and finasteride) and hair transplant is the other treatment alternative. This review surveys the evidence for low-level laser therapy (LLLT) applied to the scalp as a treatment for hair loss and discusses possible mechanisms of actions. Searches of PubMed and Google Scholar were carried out using keywords alopecia, hair loss, LLLT, photobiomodulation. Studies have shown that LLLT stimulated hair growth in mice subjected to chemotherapy-induced alopecia and also in alopecia areata. Controlled clinical trials demonstrated that LLLT stimulated hair growth in both men and women. Among various mechanisms, the main mechanism is hypothesized to be stimulation of epidermal stem cells in the hair follicle bulge and shifting the follicles into anagen phase. LLLT for hair growth in both men and women appears to be both safe and effective. The optimum wavelength, coherence and dosimetric parameters remain to be determined. © 2013 Wiley Periodicals, Inc.

Proteomic Analysis of Hair Follicles

NASA Astrophysics Data System (ADS)

Ishioka, Noriaki; Terada, Masahiro; Yamada, Shin; Seki, Masaya; Takahashi, Rika; Majima, Hideyuki J.; Higashibata, Akira; Mukai, Chiaki

2013-02-01

Hair root cells actively divide in a hair follicle, and they sensitively reflect physical conditions. By analyzing the human hair, we can know stress levels on the human body and metabolic conditions caused by microgravity environment and cosmic radiation. The Japan Aerospace Exploration Agency (JAXA) has initiated a human research study to investigate the effects of long-term space flight on gene expression and mineral metabolism by analyzing hair samples of astronauts who stayed in the International Space Station (ISS) for 6 months. During long-term flights, the physiological effects on astronauts include muscle atrophy and bone calcium loss. Furthermore, radiation and psychological effects are important issue to consider. Therefore, an understanding of the effects of the space environment is important for developing countermeasures against the effects experienced by astronauts. In this experiment, we identify functionally important target proteins that integrate transcriptome, mineral metabolism and proteome profiles from human hair. To compare the protein expression data with the gene expression data from hair roots, we developed the protein processing method. We extracted the protein from five strands of hair using ISOGEN reagents. Then, these extracted proteins were analyzed by LC-MS/MS. These collected profiles will give us useful physiological information to examine the effect of space flight.

How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse

PubMed Central

SUZUKI, Maasa; EBARA, Satomi; KOIKE, Taro; TONOMURA, Sotatsu; KUMAMOTO, Kenzo

2012-01-01

Hairs are known as a sensory apparatus for touch. Their follicles are innervated predominantly by palisade endings composed of longitudinal and circumferential lanceolate endings. However, little is known as to how their original primary neurons make up a part of the ending. In this study, innervation of the palisade endings was investigated in the auricular skin of thy1-YFP transgenic mouse. Major observations were 1) Only a small portion of PGP9.5-immunopositive axons showed YFP-positivity, 2) All of thy1-YFP-positive sensory axons were thick and myelinated, 3) Individual thy1-YFP-positive trunk axons innervated 4–54 hair follicles, 4) Most palisade endings had a gap of lanceolate ending arrangement, 5) PGP9.5-immunopositive 10–32 longitudinal lanceolate endings were closely arranged. Only a part of them were thy1-YFP-positive axons that originated from 1–3 afferents, and 6) Single nerve bundles of the dermal nerve network included both bidirectional afferents. Palisade endings innervated by multiple sensory neurons might be highly sensitive to hair movement. PMID:23229751

How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse.

PubMed

Suzuki, Maasa; Ebara, Satomi; Koike, Taro; Tonomura, Sotatsu; Kumamoto, Kenzo

2012-01-01

Hairs are known as a sensory apparatus for touch. Their follicles are innervated predominantly by palisade endings composed of longitudinal and circumferential lanceolate endings. However, little is known as to how their original primary neurons make up a part of the ending. In this study, innervation of the palisade endings was investigated in the auricular skin of thy1-YFP transgenic mouse. Major observations were 1) Only a small portion of PGP9.5-immunopositive axons showed YFP-positivity, 2) All of thy1-YFP-positive sensory axons were thick and myelinated, 3) Individual thy1-YFP-positive trunk axons innervated 4-54 hair follicles, 4) Most palisade endings had a gap of lanceolate ending arrangement, 5) PGP9.5-immunopositive 10-32 longitudinal lanceolate endings were closely arranged. Only a part of them were thy1-YFP-positive axons that originated from 1-3 afferents, and 6) Single nerve bundles of the dermal nerve network included both bidirectional afferents. Palisade endings innervated by multiple sensory neurons might be highly sensitive to hair movement.

Tβ4-overexpression based on the piggyBac transposon system in cashmere goats alters hair fiber characteristics.

PubMed

Shi, Bingbo; Ding, Qiang; He, Xiaolin; Zhu, Haijing; Niu, Yiyuan; Cai, Bei; Cai, Jiao; Lei, Anming; Kang, Danju; Yan, Hailong; Ma, Baohua; Wang, Xiaolong; Qu, Lei; Chen, Yulin

2017-02-01

Increasing cashmere yield is one of the vital aims of cashmere goats breeding. Compared to traditional breeding methods, transgenic technology is more efficient and the piggyBac (PB) transposon system has been widely applied to generate transgenic animals. For the present study, donor fibroblasts were stably transfected via a PB donor vector containing the coding sequence of cashmere goat thymosin beta-4 (Tβ4) and driven by a hair follicle-specific promoter, the keratin-associated protein 6.1 (KAP6.1) promoter. To obtain genetically modified cells as nuclear donors, we co-transfected donor vectors into fetal fibroblasts of cashmere goats. Five transgenic cashmere goats were generated following somatic cell nuclear transfer (SCNT). Via determination of the copy numbers and integration sites, the Tβ4 gene was successfully inserted into the goat genome. Histological examination of skin tissue revealed that Tβ4-overexpressing, transgenic goats had a higher secondary to primary hair follicle (S/P) ratio compared to wild type goats. This indicates that Tβ4-overexpressing goats possess increased numbers of secondary hair follicles (SHF). Our results indicate that Tβ4-overexpression in cashmere goats could be a feasible strategy to increase cashmere yield.

Innate immunity and the regulation and mobilization of keratinocyte stem cells: are the old players playing a new game?

PubMed

Singh, Ashok; Morris, Rebecca J

2012-09-01

The skin provides an anatomical barrier to physical, chemical and biological agents. Hence, it is not surprising that it has well-developed innate immunity. What we find surprising is that the CD49f(+) /CD34(+) hair follicle stem cells should have an enriched expression profile of so many genes involved in innate immunity. Do these stem cells require extra protection from environmental insults? Or, could there be a new role for these genes? To probe these questions, we first summarize the roles of some key players in epidermal innate immunity. We next focus on their expression in CD49f(+) /CD34(+) hair follicle stem cells. Then, we consider recent data suggesting a new role for these 'old players' in the regulation and mobilization of haematopoietic and mesenchymal stem cells. Finally, we hypothesize that the 'old players' in these hair follicle stem cells may be playing a 'new game'. © 2012 John Wiley & Sons A/S.

The Effect of 0.02% Mitomycin C Injection into the Hair Follicle with Radiofrequency Ablation in Trichiasis Patients

PubMed Central

Kim, Gyu-Nam; Yoo, Woong-Sun; Kim, Seong-Jae; Han, Yong-Seop; Chung, In-Young; Park, Jong-Moon; Yoo, Ji-Myong

2014-01-01

Purpose To investigate the inhibitory effect of 0.02% mitomycin C on eyelash regrowth when injected to the eyelash hair follicle immediately after radiofrequency ablation. Methods We prospectively included 21 trichiasis patients from June 2011 to October 2012. Twenty eyes of 14 patients were treated with 0.02% mitomycin C to the hair follicle immediately after radiofrequency ablation in group 1, while radiofrequency ablation only was conducted in ten eyes of seven patients in group 2. Recurrences and complications were evaluated until six months after treatment. Results One hundred sixteen eyelashes of 20 eyes in group 1 underwent treatment, and 19 (16.4%) eyelashes recurred. Eighty-four eyelashes of ten eyes in group 2 underwent treatment, and 51 (60.7%) eyelashes recurred. No patients developed any complications related to mitomycin C. Conclusions Application of 0.02% mitomycin C in conjunction with radiofrequency ablation may help to improve the success rate of radiofrequency ablation treatment in trichiasis patients. PMID:24505196

Hair-follicle Transplant Into Chronic Ulcers: A New Graft Concept.

PubMed

Martínez Martínez, M L; Escario Travesedo, E; Jiménez Acosta, F

Chronic venous leg ulcers are a major therapeutic challenge in clinical practice, and the search for new approaches to improve wound healing is essential. Many ulcers do not heal with traditional treatment using compression, debridement, and dressings. Skin-grafts variants, such as pinch grafts, punch grafts, split- or full-thickness skin grafts, and grafts derived from cells cultured in the laboratory, are among the most widely used options in ulcers that do not heal. In recent years, numerous studies have brought to our attention the important role of the hair follicle in the healing process of cutaneous wounds. Putting knowledge into practice, hair follicles from the scalp have been used in punch-type grafts transplanted to the base of chronic ulcers to stimulate healing. Results appear to be better than those with traditional hairless punch grafts, opening new lines of treatment for recalcitrant chronic venous ulcers. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Penetration of ASM 981 in canine skin: a comparative study.

PubMed

Gutzwiller, Meret E Ricklin; Reist, Martin; Persohn, Elke; Peel, John E; Roosje, Petra J

2006-01-01

ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin. To make penetration of ASM 981 visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to defrosted skin of the same dog. Using qualitative autoradiography the radioactive molecules were detected in the lumen of the hair follicles until the infundibulum, around the superficial parts of the hair follicles and into a depth of the dermis of 200 to 500 microm. Activity could not be found in deeper parts of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM 981 is low in canine skin and is only equally spread in the upper third of the dermis 24 hours after application. Penetration in frozen skin takes even longer than in living canine skin but shows the same distribution.

The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are caused by mutations in gasdermin 3.

PubMed

Runkel, F; Marquardt, A; Stoeger, C; Kochmann, E; Simon, D; Kohnke, B; Korthaus, D; Wattler, F; Fuchs, H; Hrabé de Angelis, M; Stumm, G; Nehls, M; Wattler, S; Franz, T; Augustin, M

2004-11-01

Reduced Coat 2 (Rco2) is an ENU-induced mutation affecting hair follicle morphogenesis by an abnormal and protracted catagen. We describe chromosomal mapping and molecular identification of the autosomal dominant Rco2 mutation. The Rco2 critical region on mouse chromosome 11 encompasses the alopecia loci, Bareskin (Bsk), Rex-denuded (Re(den)), Recombination induced mutation 3 (Rim3), and Defolliculated (Dfl). Recently, the gasdermin (Gsdm) gene was described as predominantly expressed in skin and gastric tissues. We provide evidence for a murine-specific gene cluster consisting of Gsdm and two closely related genes which we designate as Gsdm2 and Gsdm3. We show that Gsdm3 reflects a mutation hotspot and that Gsdm3 mutations cause alopecia in Rco2, Re(den), and Bsk mice. We infer a role of Gsdm3 during the catagen to telogen transition at the end of hair follicle morphogenesis and the formation of hair follicle-associated sebaceous glands.

Perforating folliculitis in a patient treated with nilotinib: a further evidence of C-kit involvement.

PubMed

Llamas-Velasco, Mar; Steegmann, Juan Luis; Carrascosa, Raquel; Fraga, Javier; García Diez, Amaro; Requena, Luis

2014-07-01

We present a case of perforating folliculitis in a patient treated with nilotinib, a kinase inhibitor. A 48-year-old man presented with a severely pruritic follicular rash for several months that started after reaching a complete molecular response of his myeloid chronic while treated with nilotinib. Clinical examination showed predominantly follicular pinpoint papules on trunk and proximal extremities and a biopsy showed a slightly dilated hair follicle with a focal disruption of the infundibular follicular epithelium. Other diseases related with perforating folliculitis were ruled out. The temporary relationship between the treatment and the appearance of the lesions suggests some pathogenic role of nilotinib. Relationship with nilotinib is also supported by previous similar cases related with sorafenib therapy. Both drugs inhibit c-kit and PDGF-R. PDGF-R has been previously involved in murine and human in vitro models of hair follicle cycle. So, our case supports in vivo the previous evidence of the importance of PDGF-R, a kinase, in the normal hair follicle development.

Infestivity of Demodex canis to hamster skin engrafted onto SCID mice.

PubMed

Tani, Kenji; Une, Satoshi; Hasegawa, Atsuhiko; Adachi, Makoto; Kanda, Naoko; Watanabe, Shin-ichi; Nakaichi, Munekazu; Taura, Yasuho

2005-04-01

We demonstrated that Demodex canis was transferred to skin xenografts of a dog and a hamster onto severe combined immunodeficiency mice. After the transfer of mites, the number of eggs, larvae, nymphs and adult mites per gram of canine and hamster xenografts increased, whereas no live mites were detected on murine allograft. These results indicate that D. canis proliferates in hair follicles of dog and hamster skins but not in murine allograft. Therefore, D. canis may have host preference but not strict host-specificity.

A Microarray-Based Analysis Reveals that a Short Photoperiod Promotes Hair Growth in the Arbas Cashmere Goat

PubMed Central

Guo, Jun; Wu, Dubala; Hao, Bayasihuliang; Li, Yurong; Zhao, Cunfa

2016-01-01

Many animals exhibit different behaviors in different seasons. The photoperiod can have effects on migration, breeding, fur growth, and other processes. The cyclic growth of the fur and feathers of some species of mammals and birds, respectively, is stimulated by the photoperiod as a result of hormone-dependent regulation of the nervous system. To further examine this phenomenon, we evaluated the Arbas Cashmere goat (Capra hircus), a species that is often used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclic cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Assessments of tissue sections indicated that the short photoperiod significantly induced cashmere growth. This conclusion was supported by a comparison of the differences in gene expression between the short photoperiod and natural conditions using gene chip technology. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and these genes were found to be involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages. Knowledge about differences in the expression of these genes as well as their functions and periodic regulation patterns increases our understanding of Cashmere goat hair follicle growth. This study also provides preliminary data that may be useful for the development of an artificial method to improve cashmere production by controlling the light cycle, which has practical significance for livestock breeding. PMID:26814503

Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard.

PubMed

Joseph, Laurie B; Heck, Diane E; Cervelli, Jessica A; Composto, Gabriella M; Babin, Michael C; Casillas, Robert P; Sinko, Patrick J; Gerecke, Donald R; Laskin, Debra L; Laskin, Jeffrey D

2014-06-01

Sulfur mustard (SM) is a bifunctional alkylating agent causing skin inflammation, edema and blistering. A hallmark of SM-induced toxicity is follicular and interfollicular epithelial damage. In the present studies we determined if SM-induced structural alterations in hair follicles and sebaceous glands were correlated with cell damage, inflammation and wound healing. The dorsal skin of hairless mice was treated with saturated SM vapor. One to seven days later, epithelial cell karyolysis within the hair root sheath, infundibulum and isthmus was apparent, along with reduced numbers of sebocytes. Increased numbers of utriculi, some with connections to the skin surface, and engorged dermal cysts were also evident. This was associated with marked changes in expression of markers of DNA damage (phospho-H2A.X), apoptosis (cleaved caspase-3), and wound healing (FGFR2 and galectin-3) throughout pilosebaceous units. Conversely, fatty acid synthase and galectin-3 were down-regulated in sebocytes after SM. Decreased numbers of hair follicles and increased numbers of inflammatory cells surrounding the utriculi and follicular cysts were noted within the wound 3-7 days post-SM exposure. Expression of phospho-H2A.X, cleaved caspase-3, FGFR2 and galectin-3 was decreased in dysplastic follicular epidermis. Fourteen days after SM, engorged follicular cysts which expressed galectin-3 were noted within hyperplastic epidermis. Galectin-3 was also expressed in basal keratinocytes and in the first few layers of suprabasal keratinocytes in neoepidermis formed during wound healing indicating that this lectin is important in the early stages of keratinocyte differentiation. These data indicate that hair follicles and sebaceous glands are targets for SM in the skin. Copyright © 2014 Elsevier Inc. All rights reserved.

Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy.

PubMed

Persechino, Flavia; De Carvalho, Nathalie; Ciardo, Silvana; De Pace, Barbara; Casari, Alice; Chester, Johanna; Kaleci, Shaniko; Stanganelli, Ignazio; Longo, Caterina; Farnetani, Francesca; Pellacani, Giovanni

2018-03-01

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already-described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non-melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus-like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The morphology and innervation of facial vibrissae in the tammar wallaby, Macropus eugenii.

PubMed Central

Marotte, L R; Rice, F L; Waite, P M

1992-01-01

The morphology of the vibrissal follicles on the mystacial pad of the tammar wallaby is similar to that seen in other species except that the follicles lack a ringwulst or ring sinus. Instead, the mesenchymal sheath is thickened around the central region of the hair shaft. The follicle is innervated by both deep and superficial vibrissal nerves. The deep nerve enters as 4-11 fascicles which can be in close proximity or widely distributed around the hair. C1 follicles received more myelinated nerve fibres (252 +/- 31) than the smaller C4 follicles (174 +/- 43). The deep vibrissal nerve supplies the thickened mesenchymal sheath, the narrow 'waist' region above and the majority of endings in the inner conical body (ICB), while the superficial nerves provide a sparse innervation to the ICB and rete ridge. Receptors present in the follicle were of 4 types: (1) Merkel cells, especially numerous in the outer root sheath of the 'waist' region and occasionally in the ICB and rete ridge; (2) and (3) lanceolate and lamellated endings parallel to the hair shaft in both the mesenchymal thickening and the 'waist' region where they were particularly dense; (4) free nerve endings in the mesenchymal thickening, 'waist' region and ICB. No corpuscular, bulbous or Ruffini endings were seen. The innervation of the intervibrissal fur was similar to that described in other species. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:1487434

Clinicopathologic analysis of 21 cases of nevus sebaceus: a retrospective study.

PubMed

Simi, C M; Rajalakshmi, T; Correa, Marjorie

2008-01-01

Nevus sebaceus (NS), otherwise designated as 'organoid nevus', involves proliferative changes of the sebaceous glands, sweat glands, and the hair follicles. It displays a range of appearances, depending on the lesion's age. To study the histopathological features of NS and correlate these with clinical findings. All skin biopsy specimens over a 12-year period from 1995 to 2007 which had a diagnosis of NS were included. Clinical data with follow-up notes and histopathology were reviewed. Half of the cases had a verrucous clinical appearance, while the rest presented as papules, plaques, or patches. All the cases showed immature hair follicles, and 24% of cases showed immature sebaceous glands. Normal terminal hair follicles were characteristically absent in the lesion. Nineteen percent of the cases showed dilated apocrine glands, and 14% showed hyperplasia of eccrine glands. Epidermal changes in the form of acanthosis, papillomatosis, and hyperkeratosis were seen in 86% of cases. Dilated keratin-filled infundibula were observed in 24% of cases. One case was associated with a squamous cell carcinoma. Nevus sebaceus is a cutaneous hamartoma, consisting of various elements indigenous to the organ. Normal terminal hair follicles are characteristically absent in the lesion although the same may be seen in rest of the epidermis, a feature of diagnostic importance, not usually highlighted in literature. The divergent differentiation observed in NS is consistent with the common embryologic origin of the folliculosebaceous-apocrine unit and should not mislead the pathologist.

Anti-CXCL4 monoclonal antibody accelerates telogen to anagen transition and attenuates apoptosis of the hair follicle in mice

PubMed Central

Guan, Wen; Yu, Xiaolan; Li, Jingjing; Deng, Qing; Zhang, Yang; Gao, Jing; Xia, Peng; Yuan, Yunsheng; Gao, Jin; Zhou, Liang; Han, Wei; Yu, Yan

2017-01-01

Although hair loss or alopecia is a common disease, its exact mechanisms are not yet well understood. The present study investigated the hypothesis that the homeostatic regulation of genes during hair regeneration may participate in hair loss, based on the cyclicity of hair growth. A cluster of such genes was identified by an expression gene-array from the dorsal skin in a depilated mouse model, and CXCL4 was identified as a significantly regulated gene during the hair regeneration process. To elucidate the function of CXCL4 in hair growth, CXCL4 activity was blocked by the administration of an anti-CXCL4 monoclonal antibody (mAb). Histomorphometric analysis indicated that anti-CXCL4 mAb induced an earlier anagen phase and delayed hair follicle regression, in contrast with that in the control group. Moreover, CXCL4 mAb upregulated the transcription levels of several hair growth-related genes, including Lef1, Wnt10b, Bmp4 and Bmp2. In addition, CXCL4 mAb increased the levels of the proliferation-related protein PCNA and Bcl-2 during the anagen phase, while it reduced the expression of pro-apoptotic protein Bax and cleaved caspase-3 during the catagen phase. These findings reveal that CXCL4 plays an important role in hair growth, and that blockade of CXCL4 activity promotes hair growth. PMID:28810552

Anti-CXCL4 monoclonal antibody accelerates telogen to anagen transition and attenuates apoptosis of the hair follicle in mice.

PubMed

Guan, Wen; Yu, Xiaolan; Li, Jingjing; Deng, Qing; Zhang, Yang; Gao, Jing; Xia, Peng; Yuan, Yunsheng; Gao, Jin; Zhou, Liang; Han, Wei; Yu, Yan

2017-08-01

Although hair loss or alopecia is a common disease, its exact mechanisms are not yet well understood. The present study investigated the hypothesis that the homeostatic regulation of genes during hair regeneration may participate in hair loss, based on the cyclicity of hair growth. A cluster of such genes was identified by an expression gene-array from the dorsal skin in a depilated mouse model, and CXCL4 was identified as a significantly regulated gene during the hair regeneration process. To elucidate the function of CXCL4 in hair growth, CXCL4 activity was blocked by the administration of an anti-CXCL4 monoclonal antibody (mAb). Histomorphometric analysis indicated that anti-CXCL4 mAb induced an earlier anagen phase and delayed hair follicle regression, in contrast with that in the control group. Moreover, CXCL4 mAb upregulated the transcription levels of several hair growth-related genes, including Lef1, Wnt10b, Bmp4 and Bmp2. In addition, CXCL4 mAb increased the levels of the proliferation-related protein PCNA and Bcl-2 during the anagen phase, while it reduced the expression of pro-apoptotic protein Bax and cleaved caspase-3 during the catagen phase. These findings reveal that CXCL4 plays an important role in hair growth, and that blockade of CXCL4 activity promotes hair growth.

Topical Products for Human Hair Regeneration: A Comparative Study on an Animal Model

PubMed Central

Orasan, Meda Sandra; Coneac, Andrei; Muresan, Adriana; Mihu, Carmen

2016-01-01

Background Hair loss and hair growth is the subject of tremendous amount of research. Objective This study investigated the efficacy of three chemical treatments used in humans for hair loss, using a rat model of hair regrowth. The products tested were 2% minoxidil, Hairgrow (Dar-Al-Dawa Pharma), Aminexil, Dercos (Vichy Laboratoires), and Kerium, Anti-chute (La Roche-Posay). Methods Thirty-two adult female Wistar-Bratislava rats were assigned to 4 groups. Two rectangular areas (2×4 cm) were shaved on either sides of the mid dorsal line (left side - control; right side - test area). Group I was treated topically with 2% minoxidil, group II with Aminexil, and group III with Kerium. Each rat received 0.3 ml of substance applied topically to the shaved dorsal skin every day for 28 days. Rats in group IV served as sham controls receiving no treatment. Hair regrowth was evaluated by trichoscopy (with a dermatoscope), grown hair weight (from a surface area of 1 cm2), and histopathological examination for skin thickness, follicle count, and percentage of anagen induction (morphometric assessment). Results Treatment with 2% minoxidil significantly induced hair regrowth as assessed by trichoscopy, hair weight examination, and morphometric evaluation. Hair weight examination and morphometric assessment demonstrated the lowest hair growth effect with Aminexil among the tested products. Treatment with Kerium was found to significantly induce hair regrowth (p<0.05 as compared to the control group). Conclusion Our study demonstrates that hair regrowth efficacy of products recommended for human use is not similar when tested on an animal model. PMID:26848220

A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning.

PubMed

Wang, Qixuan; Oh, Ji Won; Lee, Hye-Lim; Dhar, Anukriti; Peng, Tao; Ramos, Raul; Guerrero-Juarez, Christian Fernando; Wang, Xiaojie; Zhao, Ran; Cao, Xiaoling; Le, Jonathan; Fuentes, Melisa A; Jocoy, Shelby C; Rossi, Antoni R; Vu, Brian; Pham, Kim; Wang, Xiaoyang; Mali, Nanda Maya; Park, Jung Min; Choi, June-Hyug; Lee, Hyunsu; Legrand, Julien M D; Kandyba, Eve; Kim, Jung Chul; Kim, Moonkyu; Foley, John; Yu, Zhengquan; Kobielak, Krzysztof; Andersen, Bogi; Khosrotehrani, Kiarash; Nie, Qing; Plikus, Maksim V

2017-07-11

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.

Stem cell plasticity enables hair regeneration following Lgr5+ cell loss.

PubMed

Hoeck, Joerg D; Biehs, Brian; Kurtova, Antonina V; Kljavin, Noelyn M; de Sousa E Melo, Felipe; Alicke, Bruno; Koeppen, Hartmut; Modrusan, Zora; Piskol, Robert; de Sauvage, Frederic J

2017-06-01

Under injury conditions, dedicated stem cell populations govern tissue regeneration. However, the molecular mechanisms that induce stem cell regeneration and enable plasticity are poorly understood. Here, we investigate stem cell recovery in the context of the hair follicle to understand how two molecularly distinct stem cell populations are integrated. Utilizing diphtheria-toxin-mediated cell ablation of Lgr5 + (leucine-rich repeat-containing G-protein-coupled receptor 5) stem cells, we show that killing of Lgr5 + cells in mice abrogates hair regeneration but this is reversible. During recovery, CD34 + (CD34 antigen) stem cells activate inflammatory response programs and start dividing. Pharmacological attenuation of inflammation inhibits CD34 + cell proliferation. Subsequently, the Wnt pathway controls the recovery of Lgr5 + cells and inhibition of Wnt signalling prevents Lgr5 + cell and hair germ recovery. Thus, our study uncovers a compensatory relationship between two stem cell populations and the underlying molecular mechanisms that enable hair follicle regeneration.

Hair follicle nevus of the abdominal skin: an unusual extracephalic presentation.

PubMed

Jedrych, Jaroslaw; Akilov, Oleg; Gehris, Robin; Ho, Jonhan

2014-01-01

Hair follicle nevus (HFN) is a rare hamartoma typically diagnosed on the face of infants, where it may clinically mimic an accessory tragus. We report a 6-month-old boy who presented with a congenital fleshy, bilobed papule in the midline of his upper abdomen that upon excision was classified as an HFN based on detailed histopathologic examination. Our report documents a previously undescribed extracephalic location of the HFN and therefore expands the spectrum of clinical presentations of this rare hamartoma. © 2014 Wiley Periodicals, Inc.

Peppermint Oil Promotes Hair Growth without Toxic Signs

PubMed Central

Park, Min Ah; Kim, Young Chul

2014-01-01

Peppermint (Mentha piperita) is a plant native to Europe and has been widely used as a carminative and gastric stimulant worldwide. This plant also has been used in cosmetic formulations as a fragrance component and skin conditioning agent. This study investigated the effect of peppermint oil on hair growth in C57BL/6 mice. The animals were randomized into 4 groups based on different topical applications: saline (SA), jojoba oil (JO), 3% minoxidil (MXD), and 3% peppermint oil (PEO). The hair growth effects of the 4-week topical applications were evaluated in terms of hair growth, histological analysis, enzymatic activity of alkaline phosphatase (ALP), and gene expression of insulin-like growth factor-1 (IGF-1), known bio-markers for the enhanced hair growth. Of the 4 experimental groups, PEO group showed the most prominent hair growth effects; a significant increase in dermal thickness, follicle number, and follicle depth. ALP activity and IGF-1 expression also significantly increased in PEO group. Body weight gain and food efficiency were not significantly different between groups. These results suggest that PEO induces a rapid anagen stage and could be used for a practical agent for hair growth without change of body weight gain and food efficiency. PMID:25584150

Characteristics of MIC-1 antlerogenic stem cells and their effect on hair growth in rabbits.

PubMed

Cegielski, Marek; Izykowska, Ilona; Chmielewska, Magdalena; Dziewiszek, Wojciech; Bochnia, Marek; Calkosinski, Ireneusz; Dziegiel, Piotr

2013-01-01

We characterized growth factors produced by MIC-1 antlerogenic stem cells and attempted to apply those cells to stimulate hair growth in rabbits. We evaluated the gene and protein expression of growth factors by immunocytochemical and molecular biology techniques in MIC-1 cells. An animal model was used to assess the effects of xenogenous stem cells on hair growth. In the experimental group, rabbits were intradermally injected with MIC-1 stem cells, whereas the control group rabbits were given vehicle-only. After 1, 2 and 4 weeks, skin specimen were collected for histological and immunohistochemical tests. MIC-1 antlerogenic stem cells express growth factors, as confirmed at the mRNA and protein levels. Histological and immunohistochemical analysis demonstrated an increase in the number of hair follicles, as well as the amount of secondary hair in the follicles, without an immune response in animals injected intradermally with MIC-1 cells, compared to animals receiving vehicle-alone. MIC-1 cells accelerated hair growth in rabbits due to the activation of cells responsible for the regulation of the hair growth cycle through growth factors. Additionally, the xenogenous cell implant did not induce immune response.

The extent of the uptake of plasmid into the skin determines the immune responses induced by a DNA vaccine applied topically onto the skin

PubMed Central

Yu, Zhen; Chung, Woon-Gye; Sloat, Brian R.; Löhr, Christiane V.; Weiss, Richard; Rodriguez, B. Leticia; Li, Xinran; Cui, Zhengrong

2011-01-01

Objectives Non-invasive immunization by applying plasmid DNA topically onto the skin is an attractive immunization approach. However, the immune responses induced are generally weak. Previously, we showed that the antibody responses induced by topical DNA vaccine were significantly enhanced when hair follicles in the application area were induced into anagen (growth) stage by hair plucking. In the present study, we further investigated the mechanism of immune enhancement. Methods Three different methods, hair plucking or treatment with retinoic acid (RA) or O- tetradecanoylphorbol-13-acetate (TPA), were used to induce hair follicles into anagen stage before mice were dosed with a β-galactosidase-encoding plasmid, and the specific antibody responses induced were evaluated. Key findings The hair plucking method was more effective at enhancing the resultant antibody responses. Treatment with RA or TPA caused more damages to the skin and induced more severe local inflammations than hair plucking. However, hair plucking was most effective at enhancing the uptake or retention of the DNA in the application area. Conclusions The uptake of plasmid DNA in the application area correlated with the antibody responses induced by a topically applied DNA. PMID:21235583

Impaired hair follicle morphogenesis and polarized keratinocyte movement upon conditional inactivation of integrin-linked kinase in the epidermis.

PubMed

Nakrieko, Kerry-Ann; Welch, Ian; Dupuis, Holly; Bryce, Dawn; Pajak, Agnieszka; St Arnaud, René; Dedhar, Shoukat; D'Souza, Sudhir J A; Dagnino, Lina

2008-04-01

Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little is known about its role in epidermal development and homeostasis in vivo. We generated mice with conditional inactivation of the Ilk gene in squamous epithelia. These mice die perinatally and exhibit skin blistering and severe defects in hair follicle morphogenesis, including greatly reduced follicle numbers, failure to progress beyond very early developmental stages, and pronounced defects in follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities in adhesion to the basement membrane and in differentiation. ILK-deficient cultured keratinocytes fail to attach and spread efficiently and exhibit multiple abnormalities in actin cytoskeletal organization. Ilk gene inactivation in cultured keratinocytes causes impaired ability to form stable lamellipodia, to directionally migrate, and to polarize. These defects are accompanied by abnormal distribution of active Cdc42 to cell protrusions, as well as reduced activation of Rac1 upon induction of cell migration in scraped keratinocyte monolayers. Significantly, alterations in cell spreading and forward movement in single cells can be rescued by expression of constitutively active Rac1 or RhoG. Our studies underscore a central and distinct role for ILK in hair follicle development and in polarized cell movements, two key aspects of epithelial morphogenesis and function.

Impaired Hair Follicle Morphogenesis and Polarized Keratinocyte Movement upon Conditional Inactivation of Integrin-linked Kinase in the Epidermis

PubMed Central

Nakrieko, Kerry-Ann; Welch, Ian; Dupuis, Holly; Bryce, Dawn; Pajak, Agnieszka; St. Arnaud, René; Dedhar, Shoukat

2008-01-01

Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little is known about its role in epidermal development and homeostasis in vivo. We generated mice with conditional inactivation of the Ilk gene in squamous epithelia. These mice die perinatally and exhibit skin blistering and severe defects in hair follicle morphogenesis, including greatly reduced follicle numbers, failure to progress beyond very early developmental stages, and pronounced defects in follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities in adhesion to the basement membrane and in differentiation. ILK-deficient cultured keratinocytes fail to attach and spread efficiently and exhibit multiple abnormalities in actin cytoskeletal organization. Ilk gene inactivation in cultured keratinocytes causes impaired ability to form stable lamellipodia, to directionally migrate, and to polarize. These defects are accompanied by abnormal distribution of active Cdc42 to cell protrusions, as well as reduced activation of Rac1 upon induction of cell migration in scraped keratinocyte monolayers. Significantly, alterations in cell spreading and forward movement in single cells can be rescued by expression of constitutively active Rac1 or RhoG. Our studies underscore a central and distinct role for ILK in hair follicle development and in polarized cell movements, two key aspects of epithelial morphogenesis and function. PMID:18234842

Treatment for trichiasis through a combination of eyelash trephination and electrocautery.

PubMed

Han, Jae-Hyung; Doh, Sang-Hee

2012-05-01

This article introduces 3-mm-deep eyelash trephination combined with electrocautery as a way to increase the success rate for treatment for trichiasis. We have modified surgical instruments, ready-made ophthalmic microtrephine and cautery tip for a 3-mm-deep eyelash trephination and electrocautery. After eyelash trephination with microtrephine, electrocautery was added with a bended cautery tip after embedding in the trephination site. The trephined eyelids were photographed biweekly and checked for recurrence until 8 weeks after operation. Eyelash trephination combined with electrocautery was carried out on 20 Korean patients. The number of removed cilia was 109. Of these, the number of successfully removed hair follicles was 89. During 8 weeks, the total recurring rate of eyelash trephination combined with electrocautery was 17%. In the case of hair follicle removal success with electrocautery, the recurring rate was as low as 11%, but in the case of hair follicle removal failure with electrocautery, recurring rate is 45%. We checked the depth of removed eyelash follicles, and the mean depth was 2.03 ± 0.085 mm in this study. No serious complication was found during the period of this study. The eyelash trephination combined with electrocautery for trichiasis is a method with a low recurrence rate and few complications. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Follicular contact dermatitis revisited: A review emphasizing neomycin-associated follicular contact dermatitis

PubMed Central

Cohen, Philip R

2014-01-01

Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the PubMed database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals (including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agents-either as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions. PMID:25516854

A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair.

PubMed

Ansar, Muhammad; Raza, Syed Irfan; Lee, Kwanghyuk; Irfanullah; Shahi, Shamim; Acharya, Anushree; Dai, Hang; Smith, Joshua D; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Santos-Cortez, Regie Lyn P; Ahmad, Wasim; Leal, Suzanne M

2015-10-01

Woolly hair (WH) is a hair abnormality that is primarily characterised by tightly curled hair with abnormal growth. In two unrelated consanguineous Pakistani families with non-syndromic autosomal recessive (AR) WH, homozygosity mapping and linkage analysis identified a locus within 17q21.1-q22, which contains the type I keratin gene cluster. A DNA sample from an affected individual from each family underwent exome sequencing. A homozygous missense variant c.950T>C (p.(Leu317Pro)) within KRT25 segregated with ARWH in both families, and has a combined maximum two-point LOD score of 7.9 at ϴ=0. The KRT25 variant is predicted to result in disruption of the second α-helical rod domain and the entire protein structure, thus possibly interfering with heterodimerisation of K25 with type II keratins within the inner root sheath (IRS) of the hair follicle and the medulla of the hair shaft. Our findings implicate a novel gene involved in human hair abnormality, and are consistent with the curled, fragile hair found in mice with Krt25 mutations, and further support the role of IRS-specific type I keratins in hair follicle development and maintenance of hair texture. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

iTRAQ-Based Quantitative Proteomic Comparison of Early- and Late-Passage Human Dermal Papilla Cell Secretome in Relation to Inducing Hair Follicle Regeneration.

PubMed

Zhang, Huan; Zhu, Ning-Xia; Huang, Keng; Cai, Bo-Zhi; Zeng, Yang; Xu, Yan-Ming; Liu, Yang; Yuan, Yan-Ping; Lin, Chang-Min

2016-01-01

Alopecia is an exceedingly prevalent problem that lacks effective therapy. Recently, research has focused on early-passage dermal papilla cells (DPCs), which have hair inducing activity both in vivo and in vitro. Our previous study indicated that factors secreted from early-passage DPCs contribute to hair follicle (HF) regeneration. To identify which factors are responsible for HF regeneration and why late-passage DPCs lose this potential, we collected 48-h-culture medium (CM) from both of passage 3 and 9 DPCs, and subcutaneously injected the DPC-CM into NU/NU mice. Passage 3 DPC-CM induced HF regeneration, based on the emergence of a white hair coat, but passage 9 DPC-CM did not. In order to identify the key factors responsible for hair induction, CM from passage 3 and 9 DPCs was analyzed by iTRAQ-based quantitative proteomic technology. We identified 1360 proteins, of which 213 proteins were differentially expressed between CM from early-passage vs. late-passage DPCs, including SDF1, MMP3, biglycan and LTBP1. Further analysis indicated that the differentially-expressed proteins regulated the Wnt, TGF-β and BMP signaling pathways, which directly and indirectly participate in HF morphogenesis and regeneration. Subsequently, we selected 19 proteins for further verification by multiple reaction monitoring (MRM) between the two types of CM. These results indicate DPC-secreted proteins play important roles in HF regeneration, with SDF1, MMP3, biglycan, and LTBP1 being potential key inductive factors secreted by dermal papilla cells in the regeneration of hair follicles.

Primary cicatricial alopecia: clinical features and management.

PubMed

Ross, Elizabeth K

2007-04-01

The primary cicatricial alopecias are an uncommon, complex group of disorders that result in permanent destruction of the hair follicle, usually involving scalp hair alone. Prompt diagnosis and treatment are needed to help thwart continued hair loss and the distress that often accompanies this hair loss. Nurses can facilitate the diagnostic and treatment process and, through educational and emotionally supportive measures, have a meaningful, positive impact on the patient's well being.

Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4.

PubMed

Chen, Chih-Chiang; Murray, Philip J; Jiang, Ting Xin; Plikus, Maksim V; Chang, Yun-Ting; Lee, Oscar K; Widelitz, Randall B; Chuong, Cheng-Ming

2014-08-01

Hair cycling is modulated by factors both intrinsic and extrinsic to hair follicles. Cycling defects lead to conditions such as aging-associated alopecia. Recently, we demonstrated that mouse skin exhibits regenerative hair waves, reflecting a coordinated regenerative behavior in follicle populations. Here, we use this model to explore the regenerative behavior of aging mouse skin. Old mice (>18 months) tracked over several months show that with progressing age, hair waves slow down, wave propagation becomes restricted, and hair cycle domains fragment into smaller domains. Transplanting aged donor mouse skin to a young host can restore donor cycling within a 3 mm range of the interface, suggesting that changes are due to extracellular factors. Therefore, hair stem cells in aged skin can be reactivated. Molecular studies show that extra-follicular modulators Bmp2, Dkk1, and Sfrp4 increase in early anagen. Further, we identify follistatin as an extra-follicular modulator, which is highly expressed in late telogen and early anagen. Indeed, follistatin induces hair wave propagation and its level decreases in aging mice. We present an excitable medium model to simulate the cycling behavior in aging mice and illustrate how the interorgan macroenvironment can regulate the aging process by integrating both "activator" and "inhibitor" signals.

Sulfotransferase activity in plucked hair follicles predicts response to topical minoxidil in the treatment of female androgenetic alopecia.

PubMed

Roberts, Janet; Desai, Nisha; McCoy, John; Goren, Andy

2014-01-01

Two percent topical minoxidil is the only US Food and Drug Administration-approved drug for the treatment of female androgenetic alopecia (AGA). Its success has been limited by the low percentage of responders. Meta-analysis of several studies reporting the number of responders to 2% minoxidil monotherapy indicates moderate hair regrowth in only 13-20% of female patients. Five percent minoxidil solution, when used off-label, may increase the percentage of responders to as much as 40%. As such, a biomarker for predicting treatment response would have significant clinical utility. In a previous study, Goren et al. reported an association between sulfotransferase activity in plucked hair follicles and minoxidil response in a mixed cohort of male and female patients. The aim of this study was to replicate these findings in a well-defined cohort of female patients with AGA treated with 5% minoxidil daily for a period of 6 months. Consistent with the prior study, we found that sulfotransferase activity in plucked hair follicles predicts treatment response with 93% sensitivity and 83% specificity. Our study further supports the importance of minoxidil sulfation in eliciting a therapeutic response and provides further insight into novel targets for increasing minoxidil efficacy. © 2014 Wiley Periodicals, Inc.

Tooth, hair and claw: comparing epithelial stem cell niches of ectodermal appendages

PubMed Central

Naveau, Adrien; Seidel, Kerstin; Klein, Ophir D.

2014-01-01

The vertebrate ectoderm gives rise to organs that produce mineralized or keratinized substances, including teeth, hair, and claws. Most of these ectodermal derivatives grow continuously throughout the animal’s life and have active pools of adult stem cells that generate all the necessary cell types. These organs provide powerful systems for understanding the mechanisms that enable stem cells to regenerate or renew ectodermally derived tissues, and remarkable progress in our understanding of these systems has been made in recent years using mouse models. We briefly compare what is known about stem cells and their niches in incisors, hair follicles, and claws, and we examine expression of Gli1 as a potential example of a shared stem cell marker. We summarize some of the features, structures, and functions of the stem cell niches in these ectodermal derivatives; definition of the basic elements of the stem cell niches in these organs will provide guiding principles for identification and characterization of the niche in similar systems. PMID:24530577

Understanding and management of female pattern alopecia.

PubMed

Leavitt, Matt

2008-11-01

Female pattern hair loss is devastating to many of the 21 million U.S. women who suffer from it. It is essential to differentiate female pattern hair loss from other types of hair loss to ensure appropriate treatment. Through use of follicular units, follicular families, and follicular pairing between existing hair follicles, natural-looking results can be achieved in women. Hair transplants create the benefit of increasing density and providing options for hair styling and can be combined with medications, devices, and styling aids such as minoxidil, low-level laser therapy, and topical powder makeup, respectively.

Epidermal Cadm1 expression promotes autoimmune alopecia via enhanced T cell adhesion and cytotoxicity.

PubMed

Giangreco, Adam; Hoste, Esther; Takai, Yoshimi; Rosewell, Ian; Watt, Fiona M

2012-02-01

Autoimmune alopecia is characterized by an extensive epidermal T cell infiltrate that mediates hair follicle destruction. We have investigated the role of cell adhesion molecule 1 (Cadm1; Necl2) in this disease. Cadm1 is expressed by epidermal cells and mediates heterotypic adhesion to lymphocytes expressing class 1-restricted T cell-associated molecule (CRTAM). Using a murine autoimmune alopecia model, we observed an increase in early-activated cytotoxic (CD8-restricted, CRTAM-expressing) T cells, which preferentially associated with hair follicle keratinocytes expressing Cadm1. Coculture with Cadm1-transduced MHC-matched APCs stimulated alopecic lymph node cells to release IL-2 and IFN-γ. Overexpression of Cadm1 in cultured human keratinocytes did not promote cytokine secretion, but led to increased adhesion of alopecic cytotoxic T cells and enhanced T cell cytotoxicity in an MHC-independent manner. Epidermal overexpression of Cadm1 in transgenic mice led to increased autoimmune alopecia susceptibility relative to nontransgenic littermate controls. Our findings reveal that Cadm1 expression in the hair follicle plays a role in autoimmune alopecia.

DNA profiling in peripheral blood, buccal swabs, hair follicles and semen from a patient following allogeneic hematopoietic stem cells transplantation

PubMed Central

LI, YA-TING; XIE, MING-KUN; WU, JIN

2014-01-01

Allogeneic peripheral blood stem cells transplantation (allo-PBSCT) or allogeneic bone marrow transplantation (allo-BMT) have been widely used to treat patients exhibiting certain severe illnesses. However, previous studies have shown that the biological materials of allo-PBSCT or allo-BMT recipients may not constitute credible materials for personal identification. In the present study, four types of commonly used samples were collected from a male individual following gender-matched allo-BMT. Autosomal short tandem repeat (STR) and Y-STR markers analysis, based on polymerase chain reaction, were used to evaluate the chimerism status. The results showed that the blood sample were all donor type, the buccal swab sample were mixed chimerism, and the sperm and hair follicle samples maintained a recipient origin of 100%. In conclusion, identical results were obtained by the two methods and it was confirmed that DNA extracted from hair follicles and sperm can be used as a reference for the pre-transplant genotype DNA profile of the recipient in the gender-match allo-BMT or -PBSCT. PMID:25279149

Ghrelin in the pilosebaceous unit: alteration of ghrelin in patients with acne vulgaris.

PubMed

Cicek, Demet; Demir, Betul; Erder, Ilker; Kuloglu, Tuncay; Ucer, Ozlem; Aydin, Suleyman; Ucak, Haydar; Dertlioglu, Selma; Kalayci, Mehmet

2015-01-01

Ghrelin in the pilosebaceous tissues of human skin and ghrelin levels in patients with acne vulgaris have not yet been investigated. The purpose of this study was to screen ghrelin immunoreactivity by immunohistochemistry in human pilosebaceous tissues of human skin and also to determine the quantities of ghrelin in the serum of the patients with acne vulgaris. 30 patients presenting with acne vulgaris and 30 control subjects participated in this study. Ghrelin levels were determined by enzyme linked immunosorbent assay (ELISA). Human hair follicles and sebaceous glands were immunohistochemically examined. Immunohistochemistry results showed that there is a strong ghrelin immunoreactivity in the hair follicles and sebaceous glands in sections of human skin. The mean serum ghrelin levels (27.58 ・} 15.44 pg/mL) in patients with acne vulgaris was significantly lower than those of controls (35.62・}20.46 pg/mL). Ghrelin produced in hair follicles and sebaceous glands of the skin might participate in the pathogenesis of acne vulgaris and also acne vulgaris in humans might be associated with decreased serum ghrelin.

The Transient Role for Calcium and Vitamin D during the Developmental Hair Follicle Cycle.

PubMed

Mady, Leila J; Ajibade, Dare V; Hsaio, Connie; Teichert, Arnaud; Fong, Chak; Wang, Yongmei; Christakos, Sylvia; Bikle, Daniel D

2016-07-01

The role for 1,25-dihydroxyvitamin D3 and/or calcium in hair follicle cycling is not clear despite their impact on keratinocyte differentiation. We found that calbindin-D9k null (knockout) pups generated from calbindin-D9k knockout females fed a vitamin D-deficient, low-calcium (0.47%) diet develop transient alopecia. The pups appear phenotypically normal until 13 days of age, after which the hair progressively sheds in a caudocephalic direction, resulting in truncal alopecia totalis by 20-23 days, with spontaneous recovery by 28 days. Histological studies showed markedly dystrophic hair follicles, loss of hair shafts with increased apoptosis, and hyperplastic epidermis during this time. Ha1 expression is lost during catagen in all mice but recovers more slowly in the knockout pups on the vitamin D-deficient, low-calcium diet. Keratin 1 expression is reduced throughout days 19-28. The expressions of involucrin, loricrin, and cathepsin L is initially increased by day 19 but subsequently falls below those of controls by day 23, as does that of desmoglein 3. Feeding the mothers a high-vitamin D/high-calcium (2%)/lactose (20%) diet lessens the phenotype, and knockout pups fostered to mothers fed a normal diet do not develop alopecia. Our results show that in calbindin-D9k knockout pups, a maternal vitamin D-deficient/low-calcium diet leads to transient noncicatricial alopecia. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Nutrition and hair: deficiencies and supplements.

PubMed

Finner, Andreas M

2013-01-01

Hair follicle cells have a high turnover. A caloric deprivation or deficiency of several components, such as proteins, minerals, essential fatty acids, and vitamins, caused by inborn errors or reduced uptake, can lead to structural abnormalities, pigmentation changes, or hair loss, although exact data are often lacking. The diagnosis is established through a careful history, clinical examination of hair loss activity, and hair quality and confirmed through targeted laboratory tests. Examples of genetic hair disorders caused by reduced nutritional components are zinc deficiency in acrodermatitis enteropathica and copper deficiency in Menkes kinky hair syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Tufted hair folliculitis: a case report and literature review.

PubMed

Broshtilova, V; Bardarov, E; Kazandjieva, J; Marina, S

2011-01-01

Tufted hair folliculitis is a rare folliculitis of the scalp that resolves with patches of scarring alopecia within multiple hair tufts emerging from dilated follicular orifices. Tufting of hair is caused by clustering of adjacent follicular units due to a fibrosing process and to retention of telogen hairs within a dilated follicular orifice. Various pathogenetic mechanisms have been proposed including nevoid abnormalities, recurrent infections of the follicles, and retention of telogen hair in the tufts. We present a patient with tufted hair folliculitis who was effectively treated with antibacterial medications, verifying the infectious nature of the disease.

Epidermal dysplasia and abnormal hair follicles in transgenic mice overexpressing homeobox gene MSX-2.

PubMed

Jiang, T X; Liu, Y H; Widelitz, R B; Kundu, R K; Maxson, R E; Chuong, C M

1999-08-01

The homeobox gene Msx-2 is expressed specifically in sites of skin appendage formation. To explore its part in skin morphogenesis, we produced transgenic mice expressing Msx-2 under the control of the cytomegalovirus promoter. The skin of these transgenic mice was flaky, exhibiting desquamation and shorter hairs. Histologic analysis showed thickened epidermis with hyperproliferation, which was restricted to the basal layer. Hyperkeratosis was also evident. A wide zone of suprabasal cells were misaligned and coexpressed keratins 14 and 10. There was reduced expression of integrin beta 1 and DCC in the basal layer. Hair follicles were misaligned with a shrunken matrix region. The dermis showed increased cellularity and empty vacuoles. We suggest that Msx-2 is involved in the growth control of skin and skin appendages.

Isolation of hair follicle bulge stem cells from YFP-expressing reporter mice.

PubMed

Nakrieko, Kerry-Ann; Irvine, Timothy S; Dagnino, Lina

2013-01-01

In this article we provide a method to isolate hair follicle stem cells that have undergone targeted gene inactivation. The mice from which these cells are isolated are bred into a Rosa26-yellow fluorescent protein (YFP) reporter background, which results in YFP expression in the targeted stem cell population. These cells are isolated and purified by fluorescence-activated cell sorting, using epidermal stem cell-specific markers in conjunction with YFP fluorescence. The purified cells can be used for gene expression studies, clonogenic experiments, and biological assays, such as viability and capacity for directional migration.

Topical calcitriol enhances normal hair regrowth but does not prevent chemotherapy-induced alopecia in mice.

PubMed

Paus, R; Schilli, M B; Handjiski, B; Menrad, A; Henz, B M; Plonka, P

1996-10-01

Using a murine model that mimics chemotherapy-induced alopecia (CIA) in humans particularly well, we show here that in contrast to previously reported CIA-protective effects in neonatal rats, topical calcitriol does not prevent CIA in adolescent mice but enhances the regrowth of normally pigmented hair shafts. When, prior to injecting 1 X 120 mg/kg cyclophosphamide i.p., 0.2 microg calcitriol or vehicle alone were administered topically to the back skin of C57BL/6 mice with all hair follicles in anagen, no significant macroscopic differences in the onset and severity of CIA were seen. However, hair shaft regrowth after CIA, which is often retarded and patchy, thus displaying severe and sometimes persistent pigmentation disorders, was significantly accelerated, enhanced, and qualitatively improved in test compared with control mice. Histomorphometric analysis suggests that this is related to the fact that calcitriol-pretreated follicles favor the "dystrophic catagen pathway" of response to chemical injury, ie., a follicular repair strategy allowing for the unusually fast reconstruction of a new, undamaged anagen hair bulb. Thus, it may be unrealistic to expect that topical calcitriol can prevent human CIA, but topical calcitriols may well enhance the regrowth of a normal hair coat.

A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning

PubMed Central

Wang, Qixuan; Oh, Ji Won; Lee, Hye-Lim; Dhar, Anukriti; Peng, Tao; Ramos, Raul; Guerrero-Juarez, Christian Fernando; Wang, Xiaojie; Zhao, Ran; Cao, Xiaoling; Le, Jonathan; Fuentes, Melisa A; Jocoy, Shelby C; Rossi, Antoni R; Vu, Brian; Pham, Kim; Wang, Xiaoyang; Mali, Nanda Maya; Park, Jung Min; Choi, June-Hyug; Lee, Hyunsu; Legrand, Julien M D; Kandyba, Eve; Kim, Jung Chul; Kim, Moonkyu; Foley, John; Yu, Zhengquan; Kobielak, Krzysztof; Andersen, Bogi; Khosrotehrani, Kiarash; Nie, Qing; Plikus, Maksim V

2017-01-01

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs. DOI: http://dx.doi.org/10.7554/eLife.22772.001 PMID:28695824

Coexistence of giant blue nevus of the scalp with hair loss and alopecia areata.

PubMed

Takeichi, Sachiko; Kubo, Yoshiaki; Murao, Kazutoshi; Inoue, Natsuko; Ansai, Shin-ichi; Arase, Seiji

2011-04-01

A 43-year-old Japanese man presented with a 13-year history of a grayish macule measuring 7 cm in diameter with sparse hairs on the vertex. Histopathological examination demonstrated two types of melanocytes, spindle-shaped and ovoid cells, with abundant melanin aggregated around the upper part of the pilosebaceous apparatus. Fibrous, thick collagen bundles were also seen surrounding the upper part of the small hair follicles. There was no infiltration of melanocytes or lymphocytes in the lower dermis or adipose tissue. Based on these findings, a diagnosis of blue nevus, cellular type, was made. Giant cellular blue nevi on the scalp are rare, and 11 cases reported in the published work have shown characteristic features such as hair loss and cranial invasion of nevus cells. It should be noted that melanocytes of giant blue nevi have a high potential to damage other organs such as underlying bone and hair follicles. The patient also showed a typical lesion of alopecia areata on the left temporal which was successfully treated with topical corticosteroid. © 2010 Japanese Dermatological Association.

Panax ginseng extract antagonizes the effect of DKK-1-induced catagen-ike changes of hair follicles

PubMed Central

Lee, Yonghee; Kim, Su Na; Hong, Yong Deog; Park, Byung Cheol; Na, Yongjoo

2017-01-01

It is well known that Panax ginseng (PG) has various pharmacological effects such as anti-aging and anti-inflammation. In a previous study, the authors identified that PG extract induced hair growth by means of a mechanism similar to that of minoxidil. In the present study, the inhibitory effect of PG extract on Dickkopf-1 (DKK-1)-induced catagen-like changes in hair follicles (HFs) was investigated in addition to the underlying mechanism of action. The effects of PG extract on cell proliferation, anti-apoptotic effect, and hair growth were observed using cultured outer root sheath (ORS) keratinocytes and human HFs with or without DKK-1 treatment. The PG extract significantly stimulated proliferation and inhibited apoptosis, respectively, in ORS keratinocytes. PG extract treatment affected the expression of apoptosis-related genes Bcl-2 and Bax. DKK-1 inhibited hair growth, and PG extract dramatically reversed the effect of DKK-1 on ex vivo human hair organ culture. PG extract antagonizes DKK-1-induced catagen-like changes, in part, through the regulation of apoptosis-related gene expression in HFs. These findings suggested that PG extract may reduce hair loss despite the presence of DKK-1, a strong catagen inducer via apoptosis. PMID:28849028

Wnt1a maintains characteristics of dermal papilla cells that induce mouse hair regeneration in a 3D preculture system.

PubMed

Dong, Liang; Hao, Haojie; Liu, Jiejie; Tong, Chuan; Ti, Dongdong; Chen, Deyun; Chen, Li; Li, Meirong; Liu, Huiling; Fu, Xiaobing; Han, Weidong

2017-05-01

Hair follicle morphogenesis and regeneration depend on intensive but well-orchestrated interactions between epithelial and mesenchymal components. Therefore, an alternative strategy to reproduce the process of epithelial-mesenchymal interaction in vitro could use a 3D system containing appropriate cell populations. The 3D air-liquid culture system for reproducibly generating hair follicles from dissociated epithelial and dermal papilla (DP) cells combined with a collagen-chitosan scaffold is described in this study. Wnt-CM was prepared from the supernatant of Wnt1a-expressing bone marrow mesenchymal stem cells (BM-MSCs) that maintain the hair-inducing gene expression of DP cells. The collagen-chitosan scaffold cells (CCS cells) were constructed using a two-step method by inoculating the Wnt-CM-treated DP cells and epidermal (EP) cells into the CCS. The cells in the air-liquid culture formed dermal condensates and a proliferative cell layer in vitro. The CCS cells were able to induce hair regeneration in nude mice. The results demonstrate that Wnt-CM can maintain the hair induction ability of DP cells in expansion cultures, and this approach can be used for large-scale preparation of CCS cells in vitro to treat hair loss. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Wound healing and skin regeneration.

PubMed

Takeo, Makoto; Lee, Wendy; Ito, Mayumi

2015-01-05

The skin is a complex organ consisting of the epidermis, dermis, and skin appendages, including the hair follicle and sebaceous gland. Wound healing in adult mammals results in scar formation without any skin appendages. Studies have reported remarkable examples of scarless healing in fetal skin and appendage regeneration in adult skin following the infliction of large wounds. The models used in these studies have offered a new platform for investigations of the cellular and molecular mechanisms underlying wound healing and skin regeneration in mammals. In this article, we will focus on the contribution of skin appendages to wound healing and, conversely, skin appendage regeneration following injuries. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Cashmere growth control in Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 and decorin genes

PubMed Central

2018-01-01

Objective The study investigated the biological functions and mechanisms for controlling cashmere growth of Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) and decorin (DCN) genes. Methods cDNA library of Liaoning cashmere goat was constructed in early stages. OCIAD2 and DCN genes related to cashmere growth were identified by homology analysis comparison. The expression location of OCIAD2 and DCN genes in primary and secondary hair follicles (SF) was performed using in situ hybridization. The expression of OCIAD2 and DCN genes in primary and SF was performed using real-time polymerase chain reaction (PCR). Results In situ hybridization revealed that OCIAD2 and DCN were expressed in the inner root sheath of Liaoning cashmere goat hair follicles. Real-time quantitative PCR showed that these genes were highly expressed in SF during anagen, while these genes were highly expressed in primary hair follicle in catagen phase. Melatonin (MT) inhibited the expression of OCIAD2 and promoted the expression of DCN. Insulin-like growth factors-1 (IGF-1) inhibited the expression of OCIAD2 and DCN, while fibroblast growth factors 5 (FGF5) promoted the expression of these genes. MT and IGF-1 promoted OCIAD2 synergistically, while MT and FGF5 inhibited the genes simultaneously. MT+IGF-1/MT+FGF5 inhibited DCN gene. RNAi technology showed that OCIAD2 expression was promoted, while that of DCN was inhibited. Conclusion Activation of bone morphogenetic protein (BMP) signaling pathway up-regulated OCIAD2 expression and stimulated SF to control cell proliferation. DCN gene affected hair follicle morphogenesis and periodic changes by promoting transforming growth factor-β (TGF-β) and BMP signaling pathways. OCIAD2 and DCN genes have opposite effects on TGF-β signaling pathway and inhibit each other to affect the hair growth. PMID:29514440

Topical liposomal Rose Bengal for photodynamic white hair removal: randomized, controlled, double-blind study.

PubMed

Samy, Nevien; Fadel, Maha

2014-04-01

Blond and white hair removal by laser is a complicated task with weak satisfactory results due to the deficiency in laser-absorbing chromophore. To investigate if repetitive sessions of photodynamic therapy (PDT) using external application of liposomal Rose bengal (RB) photosensitizer followed by intense pulsed light (IPL) exposure enables removal of gray and white hair. Rose bengal loaded in liposomes (LRB) was constructed, prepared in hydrogel, and was studied for some pharmaceutical properties. Penetration and selective hair follicle damage in mice skin were studied. Topical gel containing LRB was used for treating fifteen adult females who were complaining of facial white terminal hair. Unwanted facial hair was treated for three sessions at intervals of 4-6 weeks using intense pulsed light (IPL). At each session, the treatment area was pre-treated with topical LRB gel, while a control group of another 15 patients applied placebo gel before IPL treatment. Evaluations included hair regrowth, which was measured 4 weeks after each treatment session and at 6 months follow-up by counting the number of terminal hair compared with baseline pretreatment values. Treatment outcomes and complications if any were also reported. Average hair regrowth in the LRB group was 56% after 3 treatment cycles. After six-months follow up, average terminal hair count compared with baseline pretreatment showed 40% reduction and no recorded side effects. A significant difference (P<0.05) was seen compared with the control group; the clinical results were promising. Photodynamic hair removal using rose bengal-encapsulated liposomal gel in combination with IPL treatment showed significant efficacy in the treatment of white hair compared with a control group.

The topical penta-peptide Gly-Pro-Ile-Gly-Ser increases the proportion of thick hair in Japanese men with androgenetic alopecia.

PubMed

Iwabuchi, Tokuro; Takeda, Shunsuke; Yamanishi, Haruyo; Ideta, Ritsuro; Ehama, Ritsuko; Tsuruda, Akinori; Shibata, Hideaki; Ito, Tomoko; Komatsu, Nobuyuki; Terai, Keiko; Oka, Syuichi

2016-06-01

A penta-peptide, Gly-Pro-Ile-Gly-Ser (GPIGS), promotes proliferation of mouse hair keratinocytes and accelerates hair growth in mice. This study focused on the ability of the peptide to promote human hair growth. We used a human hair keratinocyte proliferation assay and organ cultures of human hair follicle as in vitro systems. The lotions with and without the penta-peptide were administered to 22 Japanese men with androgenetic alopecia (AGA) for 4 months in a double-blind and randomized clinical study. The penta-peptide significantly stimulated the proliferation of human hair keratinocytes at a concentration of 2.3 μm (P < 0.01), and 5.0 μm of this peptide had a marked effect on hair shaft elongation in the organ culture (P < 0.05). The change in the proportion of thick hair (≥60 μm) compared to baseline in patients that received the peptide was significantly higher than in the placebo (P = 0.006). The change in the proportion of vellus hair (<40 μm) was also significantly lower in the peptide group than in the placebo (P = 0.029). The penta-peptide also significantly improved the appearance of baldness (P = 0.020) when blinded reviewers graded photographs of the participants according to a standardized baldness scale. No adverse dermatological effects due to treatment were noted during this clinical study. This penta-peptide promotes proliferation of human hair keratinocytes and hair shaft elongation of human hair follicles, in vitro. This peptide increases thick hair ratio in vivo, and this compound is useful for the improvement of AGA. © 2016 Wiley Periodicals, Inc.

Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation

PubMed Central

Murgiano, Leonardo; Shirokova, Vera; Welle, Monika Maria; Jagannathan, Vidhya; Plattet, Philippe; Oevermann, Anna; Pienkowska-Schelling, Aldona; Gallo, Daniele; Gentile, Arcangelo; Mikkola, Marja; Drögemüller, Cord

2015-01-01

Four related cows showed hairless streaks on various parts of the body with no correlation to the pigmentation pattern. The stripes occurred in a consistent pattern resembling the lines of Blaschko. The non-syndromic hairlessness phenotype observed occurred across three generations of a single family and was compatible with an X-linked mode of inheritance. Linkage analysis and subsequent whole genome sequencing of one affected female identified two perfectly associated non-synonymous sequence variants in the critical interval on bovine chromosome X. Both variants occurred in complete linkage disequilibrium and were absent in more than 3900 controls. An ERCC6L missense mutation was predicted to cause an amino acid substitution of a non-conserved residue. Analysis in mice showed no specific Ercc6l expression pattern related to hair follicle development and therefore ERCC6L was not considered as causative gene. A point mutation at the 5'-splice junction of exon 5 of the TSR2, 20S rRNA accumulation, homolog (S. cerevisiae), gene led to the production of two mutant transcripts, both of which contain a frameshift and generate a premature stop codon predicted to truncate approximately 25% of the protein. Interestingly, in addition to the presence of both physiological TSR2 transcripts, the two mutant transcripts were predominantly detected in the hairless skin of the affected cows. Immunohistochemistry, using an antibody against the N-terminal part of the bovine protein demonstrated the specific expression of the TSR2 protein in the skin and the hair of the affected and the control cows as well as in bovine fetal skin and hair. The RNA hybridization in situ showed that Tsr2 was expressed in pre- and post-natal phases of hair follicle development in mice. Mammalian TSR2 proteins are highly conserved and are known to be broadly expressed, but their precise in vivo functions are poorly understood. Thus, by dissecting a naturally occurring mutation in a domestic animal species, we identified TSR2 as a regulator of hair follicle development. PMID:26203908

The dog mite, Demodex canis: prevalence, fungal co-infection, reactions to light, and hair follicle apoptosis.

PubMed

Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

2011-01-01

Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3.

The Dog Mite, Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis

PubMed Central

Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

2011-01-01

Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3. PMID:21867442

[Contribution to one world, one health: a dog with demodicosis.].

PubMed

Beyazit, Ayşen; Inceboz, Tonay; Over, Leyla

2010-01-01

Dogs are the most preferred pet animal in the world. Canine demodicosis is a skin disease of dogs in which there is proliferation of Demodex canis, an acarine parasite of canine hair follicles, and is typically manifested by alopecia as well as inflammation of hair follicles and sebaceous glands. Secondary bacterial infection often induces pustule and a crusting dermatitis. Two years ago, a police dog eight years old, without any previous health problem, was brought to a private veterinary clinic for edematous and inflammatory lesions on the soles of its feet. In the clinic, antibacterial and antimicotics were applied for treatment of the lesions, but ten months after completion of the therapy the lesions relapsed and the treatment was repeated. But again six months after the last treatment, the lesions spread widely and the general health status of the dog began to worsen. Finally the dog was brought for treatment to the Izmir Bornova Veterinary Research Institution. Microscopic examination of all the skin scrapings revealed the presence of 10-15 adult Demodex mites per cm(2) and the diagnosis was pododemodicosis. Treatment was performed with ivermectin, antibacterial drugs and beta-glucan. The density of Demodex was reduced after two months of therapy and there was clinical and microscopical improvement. Six months after completion of the therapy the lesions disappeared completely.

Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia

PubMed Central

Garza, Luis A.; Liu, Yaping; Yang, Zaixin; Alagesan, Brinda; Lawson, John A.; Norberg, Scott M.; Loy, Dorothy E.; Zhao, Tailun; Blatt, Hanz B.; Stanton, David C.; Carrasco, Lee; Ahluwalia, Gurpreet; Fischer, Susan M.; FitzGerald, Garret A.; Cotsarelis, George

2012-01-01

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein (heterotrimeric guanine nucleotide)–coupled receptor 44 (GPR44), but not the PGD2 receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment. PMID:22440736

Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture.

PubMed

Kloepper, Jennifer Elisabeth; Sugawara, Koji; Al-Nuaimi, Yusur; Gáspár, Erzsébet; van Beek, Nina; Paus, Ralf

2010-03-01

The organ culture of human scalp hair follicles (HFs) is the best currently available assay for hair research in the human system. In order to determine the hair growth-modulatory effects of agents in this assay, one critical read-out parameter is the assessment of whether the test agent has prolonged anagen duration or induced catagen in vitro. However, objective criteria to distinguish between anagen VI HFs and early catagen in human HF organ culture, two hair cycle stages with a deceptively similar morphology, remain to be established. Here, we develop, document and test an objective classification system that allows to distinguish between anagen VI and early catagen in organ-cultured human HFs, using both qualitative and quantitative parameters that can be generated by light microscopy or immunofluorescence. Seven qualitative classification criteria are defined that are based on assessing the morphology of the hair matrix, the dermal papilla and the distribution of pigmentary markers (melanin, gp100). These are complemented by ten quantitative parameters. We have tested this classification system by employing the clinically used topical hair growth inhibitor, eflornithine, and show that eflornithine indeed produces the expected premature catagen induction, as identified by the novel classification criteria reported here. Therefore, this classification system offers a standardized, objective and reproducible new experimental method to reliably distinguish between human anagen VI and early catagen HFs in organ culture.

The Significance of Scalp Involvement in Pemphigus: A Literature Review

PubMed Central

Sar-Pomian, Marta; Rudnicka, Lidia

2018-01-01

Scalp is a unique location for pemphigus because of the abundance of desmogleins localized in hair follicles. Scalp involvement is observed in up to 60% of patients in the course of pemphigus. The lesions may occasionally lead to alopecia. Unforced removal of anagen hairs in a pull test is a sign of high disease activity. Direct immunofluorescence of plucked hair bulbs is considered a reliable diagnostic method in patients with pemphigus. Follicular acantholysis is a characteristic histopathological feature of pemphigus lesions localized on the scalp. Trichoscopy may serve as a supplementary method in the diagnosis of pemphigus. This review summarizes the most recent data concerning scalp involvement in pemphigus vulgaris and pemphigus foliaceus. A systematic literature search was conducted in three medical databases: PubMed, Embase, and Web of Science. The analysis included literature data about desmoglein distribution in hair follicles, as well as information about clinical manifestations, histopathology, immunopathology, and trichoscopy of scalp lesions in pemphigus and their response to treatment. PMID:29770335

Differential diagnosis of the scalp hair folliculitis.

PubMed

Lugović-Mihić, Liborija; Barisić, Freja; Bulat, Vedrana; Buljan, Marija; Situm, Mirna; Bradić, Lada; Mihić, Josip

2011-09-01

Scalp hair folliculitis is a relatively common condition in dermatological practice and a major diagnostic and therapeutic challenge due to the lack of exact guidelines. Generally, inflammatory diseases of the pilosebaceous follicle of the scalp most often manifest as folliculitis. There are numerous infective agents that may cause folliculitis, including bacteria, viruses and fungi, as well as many noninfective causes. Several noninfectious diseases may present as scalp hair folliculitis, such as folliculitis decalvans capillitii, perifolliculitis capitis abscendens et suffodiens, erosive pustular dermatitis, lichen planopilaris, eosinophilic pustular folliculitis, etc. The classification of folliculitis is both confusing and controversial. There are many different forms of folliculitis and several classifications. According to the considerable variability of histologic findings, there are three groups of folliculitis: infectious folliculitis, noninfectious folliculitis and perifolliculitis. The diagnosis of folliculitis occasionally requires histologic confirmation and cannot be based solely on clinical appearance of scalp lesions. This article summarizes prominent variants of inflammatory diseases of the scalp hair follicle with differential diagnosis and appertaining histological features.

Functional assessment of a novel COL4A5 splice region variant and immunostaining of plucked hair follicles as an alternative method of diagnosis in X-linked Alport syndrome.

PubMed

Malone, Andrew F; Funk, Steven D; Alhamad, Tarek; Miner, Jeffrey H

2017-06-01

Many COL4A5 splice region variants have been described in patients with X-linked Alport syndrome, but few have been confirmed by functional analysis to actually cause defective splicing. We sought to demonstrate that a novel COL4A5 splice region variant in a family with Alport syndrome is pathogenic using functional studies. We also describe an alternative method of diagnosis. Targeted next-generation sequencing results of an individual with Alport syndrome were analyzed and the results confirmed by Sanger sequencing in family members. A splicing reporter minigene assay was used to examine the variant's effect on splicing in transfected cells. Plucked hair follicles from patients and controls were examined for collagen IV proteins using immunofluorescence microscopy. A novel splice region mutation in COL4A5, c.1780-6T>G, was identified and segregated with disease in this family. This variant caused frequent skipping of exon 25, resulting in a frameshift and truncation of collagen α5(IV) protein. We also developed and validated a new approach to characterize the expression of collagen α5(IV) protein in the basement membranes of plucked hair follicles. Using this approach we demonstrated reduced collagen α5(IV) protein in affected male and female individuals in this family, supporting frequent failure of normal splicing. Differing normal to abnormal transcript ratios in affected individuals carrying splice region variants may contribute to variable disease severity observed in Alport families. Examination of plucked hair follicles in suspected X-linked Alport syndrome patients may offer a less invasive alternative method of diagnosis and serve as a pathogenicity test for COL4A5 variants of uncertain significance.

Functional assessment of a novel COL4A5 splice region variant and immunostaining of plucked hair follicles as an alternative method of diagnosis in X-linked Alport syndrome

PubMed Central

Malone, Andrew F.; Funk, Steven D.; Alhamad, Tarek; Miner, Jeffrey H.

2016-01-01

Introduction Many COL4A5 splice region variants have been described in patients with X-linked Alport syndrome, but few have been confirmed by functional analysis to actually cause defective splicing. We sought to demonstrate that a novel COL4A5 splice region variant in a family with Alport syndrome is pathogenic using functional studies. We also describe an alternative method of diagnosis. Methods We analyzed targeted next-generation sequencing results of an individual with Alport syndrome and confirmed results by Sanger sequencing in family members. A splicing reporter minigene assay was used to examine the variant’s effect on splicing in transfected cells. Plucked hair follicles from patients and controls were examined for collagen IV proteins using immunofluorescence microscopy. Results A novel splice region mutation in COL4A5, c.1780-6T>G, was identified and segregated with disease in this family. This variant caused frequent skipping of exon 25, resulting in a frameshift and truncation of collagen α5(IV) protein. We also developed and validated a new approach to characterize the expression of collagen α5(IV) protein in the basement membranes of plucked hair follicles. We demonstrated reduced collagen α5(IV) protein in affected male and female individuals in this family, supporting frequent failure of normal splicing. Conclusions Differing normal to abnormal transcript ratios in affected individuals carrying splice region variants may contribute to variable disease severity observed in Alport families. Examination of plucked hair follicles in suspected X-linked Alport syndrome patients may offer a less invasive alternative method of diagnosis and serve as a pathogenicity test for COL4A5 variants of uncertain significance. PMID:28013382

Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism.

PubMed

Luanpitpong, Sudjit; Nimmannit, Ubonthip; Chanvorachote, Pithi; Leonard, Stephen S; Pongrakhananon, Varisa; Wang, Liying; Rojanasakul, Yon

2011-08-01

Induction of massive apoptosis of hair follicle cells by chemotherapy has been implicated in the pathogenesis of chemotherapy-induced alopecia (CIA), but the underlying mechanisms of regulation are not well understood. The present study investigated the apoptotic effect of cisplatin in human hair follicle dermal papilla cells and HaCaT keratinocytes, and determined the identity and role of specific reactive oxygen species (ROS) involved in the process. Treatment of the cells with cisplatin induced ROS generation and a parallel increase in caspase activation and apoptotic cell death. Inhibition of ROS generation by antioxidants inhibited the apoptotic effect of cisplatin, indicating the role of ROS in the process. Studies using specific ROS scavengers further showed that hydroxyl radical, but not hydrogen peroxide or superoxide anion, is the primary oxidative species responsible for the apoptotic effect of cisplatin. Electron spin resonance studies confirmed the formation of hydroxyl radicals induced by cisplatin. The mechanism by which hydroxyl radical mediates the apoptotic effect of cisplatin was shown to involve down-regulation of the anti-apoptotic protein Bcl-2 through ubiquitin-proteasomal degradation. Bcl-2 was also shown to have a negative regulatory role on hydroxyl radical. Together, our results indicate an essential role of hydroxyl radical in cisplatin-induced cell death of hair follicle cells through Bcl-2 regulation. Since CIA is a major side effect of cisplatin and many other chemotherapeutic agents with no known effective treatments, the knowledge gained from this study could be useful in the design of preventive treatment strategies for CIA through localized therapy without compromising the chemotherapy efficacy.

DETERMINATION OF MERCURY IN HAIR OF CHILDREN.

PubMed

Pino, A; Bocca, B; Forte, G; Majorani, C; Petrucci, F; Senofonte, O; Alimonti, A

2018-06-25

Although high or repeated exposure to different forms of Hg can have serious health consequences, the most important toxicity risk for humans is as methylmercury (MeHg) which exposure is mainly through consumption of fish. Generally, more than the 80% of Hg in hair is as MeHg, which is taken up by hair follicles as MeHg-cysteine complexes. In this context, hair samples were collected from 200 children (7 years) living in a site in the North East (A) and from 299 children (6-11 years) living in a urban area of South Italy (B) to determine the levels of MeHg. Considering the neurotoxicity of MeHg, children were subjected to cognitive and neuropsychological tests. The hair values of Hg in the children population groups were comparable with data reported in other international surveys. On the other hand, combining results of the neurological tests with Hg levels, a possible relationship between Hg and an increase of the errors average reported in some neurological has been noted. Although the Hg levels were not elevated, a possible neurological influence in children, a population more susceptible than adults, might not be excluded. But the influence on neurological performances of the children could be also due to the family environment (socio economic status, educational level, etc.). Copyright © 2018. Published by Elsevier B.V.

Ingrowing Hair

PubMed Central

Luo, Di-Qing; Liang, Yu-Hua; Li, Xi-Qing; Zhao, Yu-Kun; Wang, Fang; Sarkar, Rashmi

2016-01-01

Abstract Cutaneous pili migrans and creeping eruption caused by parasitic diseases may present as a moving linear lesion in skin. The former, caused by a hair shaft or fragment embedded in the superficial skin or middle dermis, is a rare condition characterized by creeping eruption with a black line observed at the advancing end. In exceptionally rare instance, the hair grows inside the skin and burrows in the uppermost dermis, such a condition has been called “ingrown hair.” We report a 30-year-old Chinese man, who was accustomed to pull or extrude the beard hairs, with 1-year history of slowly extending black linear eruption on his right chin. Cutaneous examination revealed a 4-cm long black linear lesion beneath the skin associated with edematous erythema around and folliculitis on both ends of the lesion. After treatment with topical mupirocin ointment, the erythema and folliculitis improved and 2 hairs of the beard with hair follicles were pulled out from the skin. Two weeks later, another similar black line about 1 cm in length in the skin presented on the prior lesional area, which was pulled out by a shallow incision of the skin and was also demonstrated as a beard hair with hair follicle. The patient was diagnosed as “ingrowing hair” with multiple recurrences. The lesions recovered after the beard hairs were pulled out. No recurrence occurred in a year of follow-up. We suggest that “ingrowing hair” is better than “ingrown hair” to describe such a condition. Pulling out the involved hair and correcting the bad practice are its optimal management strategies. PMID:27175694

Eruptive vellus hair cysts: report of a pediatric case with partial response to calcipotriene therapy.

PubMed

Erkek, Emel; Kurtipek, Gülcan Saylam; Duman, Deniz; Sanli, Cihat; Erdoğan, Sibel

2009-12-01

Eruptive vellus hair cysts (EVHCs) are characterized by asymptomatic, follicular, comedonelike papules usually located on the anterior chest and abdomen. We present a pediatric case of EVHC associated with attention deficit hyperactivity disorder that partially responded to calcipotriene cream within 2 months. Our aim is to refamiliarize clinicians with a common albeit frequently unrecognized disorder of vellus hair follicles.

Targeted disruption of glutathione peroxidase 4 (GPx4) in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2

PubMed Central

Sengupta, Aniruddha; Lichti, Ulrike F.; Carlson, Bradley A.; Cataisson, Christophe; Ryscavage, Andrew O.; Mikulec, Carol; Conrad, Marcus; Fischer, Susan M.; Hatfield, Dolph L.; Yuspa, Stuart H.

2013-01-01

Selenoproteins are essential molecules for the mammalian antioxidant network. We previously demonstrated that targeted loss of all selenoproteins in mouse epidermis disrupted skin and hair development and caused premature death. In the current study we targeted specific selenoproteins for epidermal deletion to determine whether similar phenotypes developed. Keratinocyte-specific knockout mice lacking either the glutathione peroxidase 4 (GPx4) or thioredoxin reductase 1 (TR1) gene were generated by cre-lox technology using K14-cre. TR1 knockout mice had a normal phenotype in resting skin while GPx4 loss in epidermis caused epidermal hyperplasia, dermal inflammatory infiltrate, dysmorphic hair follicles and alopecia in perinatal mice. Unlike epidermal ablation of all selenoproteins, mice ablated for GPx4 recovered after 5 weeks and had a normal lifespan. GPx1 and TR1 were upregulated in the skin and keratinocytes of GPx4 knockout mice. GPx4 deletion reduces keratinocyte adhesion in culture and increases lipid peroxidation and COX-2 levels in cultured keratinocytes and whole skin. Feeding a COX-2 inhibitor to nursing mothers partially prevents development of the abnormal skin phenotype in knockout pups. These data link the activity of cutaneous GPx4 to the regulation of COX-2 and hair follicle morphogenesis and provide insight into the function of individual selenoprotein activity in maintaining cutaneous homeostasis. PMID:23364477

Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin.

PubMed

Qiao, W; Li, A G; Owens, P; Xu, X; Wang, X-J; Deng, C-X

2006-01-12

Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.

Establishment and characterization of outer root sheath (ORS) cell line from Jining grey goat.

PubMed

Cui, Zhifeng; Hu, Yanxia; Wang, Hui; Zeng, Yongqing; Dong, Bin; Zhu, Houshun; Dong, Zhongdian; Liu, Zhiyuan

2012-03-01

A new line of outer root sheath (ORS) cells was established from hair follicles of Jining grey goat by using a mechanical separation combined with enzyme digestion. Cell morphology is described at different phases. The chromosome analysis of ORS cells, identification of the ORS cells and morphological reversion test were detected at the 4th and 40th passages. The ORS cells were healthy and the growth characteristics were stable with a population doubling time of 52 h. Chromosome analysis showed that >58% of cells were diploid. Test for ORS cell line CK19 expression was positive. This newly established ORS cell line not only lays the foundation for further studying on the growth, regeneration, development law of goat hair follicle but also provides a mirror for the research of human hair in medical field.

Gene Expression Profiling of the Intact Dermal Sheath Cup of Human Hair Follicles.

PubMed

Niiyama, Shiro; Ishimatsu-Tsuji, Yumiko; Nakazawa, Yosuke; Yoshida, Yuzo; Soma, Tsutomu; Ideta, Ritsuro; Mukai, Hideki; Kishimoto, Jiro

2018-04-24

Cells that constitute the dermal papillae of hair follicles might be derived from the dermal sheath, the peribulbar component of which is the dermal sheath cup. The dermal sheath cup is thought to include the progenitor cells of the dermal papillae and possesses hair inductive potential; however, it has not yet been well characterized. This study investigated the gene expression profile of the intact dermal sheath cup, and identified dermal sheath cup signature genes, including extracellular matrix components and BMP-binding molecules, as well as TGF-b1 as an upstream regulator. Among these, GREM2, a member of the BMP antagonists, was found by in situ hybridization to be highly specific to the dermal sheath cup, implying that GREM2 is a key molecule contributing to maintenance of the properties of the dermal sheath cup.

Hair-growth-promoting effect of conditioned medium of high integrin α6 and low CD 71 (α6bri/CD71dim) positive keratinocyte cells.

PubMed

Won, Chong Hyun; Jeong, Yun-Mi; Kang, Sangjin; Koo, Tae-Sung; Park, So-Hyun; Park, Ki-Young; Sung, Young-Kwan; Sung, Jong-Hyuk

2015-02-19

Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor). A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells.

The male beard hair and facial skin - challenges for shaving.

PubMed

Maurer, M; Rietzler, M; Burghardt, R; Siebenhaar, F

2016-06-01

The challenge of shaving is to cut the beard hair as closely as possible to the skin without unwanted effects on the skin. To achieve this requires the understanding of beard hair and male facial skin biology as both, the beard hair and the male facial skin, contribute to the difficulties in obtaining an effective shave without shaving-induced skin irritation. Little information is available on the biology of beard hairs and beard hair follicles. We know that, in beard hairs, the density, thickness, stiffness, as well as the rates of elliptical shape and low emerging angle, are high and highly heterogeneous. All of this makes it challenging to cut it, and shaving techniques commonly employed to overcome these challenges include shaving with increased pressure and multiple stroke shaving, which increase the probability and extent of shaving-induced skin irritation. Several features of male facial skin pose problems to a perfect shave. The male facial skin is heterogeneous in morphology and roughness, and male skin has a tendency to heal slower and to develop hyperinflammatory pigmentation. In addition, many males exhibit sensitive skin, with the face most often affected. Finally, the hair follicle is a sensory organ, and the perifollicular skin is highly responsive to external signals including mechanical and thermal stimulation. Perifollicular skin is rich in vasculature, innervation and cells of the innate and adaptive immune system. This makes perifollicular skin a highly responsive and inflammatory system, especially in individuals with sensitive skin. Activation of this system, by shaving, can result in shaving-induced skin irritation. Techniques commonly employed to avoid shaving-induced skin irritation include shaving with less pressure, pre- and post-shave skin treatment and to stop shaving altogether. Recent advances in shaving technology have addressed some but not all of these issues. A better understanding of beard hairs, beard hair follicles and male facial skin is needed to develop novel and better approaches to overcome the challenge of shaving. This article covers what is known about the physical properties of beard hairs and skin and why those present a challenge for blade and electric shaving, respectively. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

[Current Topics on Vitamin D. The vitamin D functions in keratinocytes and its therapeutic applications].

PubMed

Sawatsubashi, Shun

2015-03-01

1,25 (OH) 2D and calcium have been shown to promote epidermal keratinocyte differentiation and prevent proliferation. These prodifferentiation and antiproliferative effects of 1,25 (OH) 2D have led to its clinical use in the treatment of psoriasis. However, the mechanism of vitamin D action on keratinocytes remains largely unknown. While the actions of calcium and the vitamin D receptor signaling pathways on epidermal keratinocyte differentiation are redundant, their effects on the hair follicle are not. In this review, we discuss how the vitamin D and its receptor contribute to skin and hair follicle homeostasis.

The hair follicle mites (Demodex spp.). Could they be vectors of pathogenic microorganisms?

PubMed

Wolf, R; Ophir, J; Avigad, J; Lengy, J; Krakowski, A

1988-01-01

The hair follicle mites Demodex folliculorum and D. brevis are the most common permanent ectoparasites of Man. Ordinarily they are harmless to their human host and appear to be of no medical significance. We present, however, an unusual finding regarding this mite, namely, that in a potassium hydroxide mount of a skin scraping from a mycotic plaque we found numerous Demodex mites containing inside them spores of Microsporum canis. This could mean that the putatively inoffensive Demodex has the potential to ingest various microorganisms that are found in its niche and transport them to other areas of the skin or possibly to other individuals.

Pseudomonas folliculitis in Arabian baths.

PubMed

Molina-Leyva, Alejandro; Ruiz-Ruigomez, Maria

2013-07-14

A 35-year-old man presented with a painful cutaneous skin eruption that was localized on the upper trunk. He stated that the previous weekend he had attended an Arabian bath. The physical examination revealed multiple hair follicle-centered papulopustules surrounded by an erythematous halo. A clinical diagnosis of pseudomonas folliculitis was made and treatment was prescribed. Afterwards Pseudomonas aeruginosa was isolated from a pustule culture. Pseudomonas folliculitis is a bacterial infection of the hair follicles. The most common reservoirs include facilities with hot water and complex piping systems that are difficult to clean, such as hot tubs and bathtubs. Despite adequate or high chlorine levels, Pseudomonas aeruginosa can grow within a biofilm.

Investigation of Hair Follicle and Plasma Biomarkers for Low-Level VX Vapor Exposure

DTIC Science & Technology

2006-11-01

hydroxyxanthotoxin L-Methionine response 5 Poly- L – Glutamate L-Valine Pyridoxal 2-Naphthylamine Uridine 4- oxoproline L-Citrulline e 5 ...verified in the bulb region of the follicle except Na+/K+-ATPase α1. Figure 1. 5 Figure 1: Western Blot of total rat follicle bulb...protein separated by 10-20% SDS-PAGE. The lanes are: 1: BioRad Kaleidoscope Molecular Weight Ladder; 2: BRCA 1; 3: GAPDH; 4: Keratin 10; 5

Triggered release of model drug from AuNP-doped BSA nanocarriers in hair follicles using IRA radiation.

PubMed

Lademann, J; Richter, H; Knorr, F; Patzelt, A; Darvin, M E; Rühl, E; Cheung, K Y; Lai, K K; Renneberg, R; Mak, W C

2016-01-01

Recent advances in the field of dermatotherapy have resulted in research efforts focusing on the use of particle-based drug delivery systems for the stimuli-responsive release of drugs in the skin and skin appendages, i.e. hair follicles and sebaceous glands. However, effective and innocuous trigger mechanisms which result in the release of the drugs from the nanocarriers upon reaching the target structures are still lacking. For the first time, the present study demonstrated the photo-activated release of the model drug fluorescein isothiocyanate (FITC) from topically applied gold nanoparticle-doped bovine serum albumin (AuNPs-doped BSA) particles (approx. 545nm) using water-filtered infrared A (IRA) radiation in the hair follicles of an ex vivo porcine skin model. The IRA radiation-induced plasmonic heating of the AuNPs results in the partial decomposition or opening of the albumin particles and release the model drug, while control particles without AuNPs show insignificant release. The results demonstrate the feasibility of using IRA radiation to induce release of encapsulated drugs from plasmonic nanocarriers for the targeting of follicular structures. However, the risk of radiation-induced skin damage subsequent to repeated applications of high infrared dosages may be significant. Future studies should aim at determining the suitability of lower infrared A dosages, such as for medical treatment regimens which may necessitate repeated exposure to therapeutics. Follicular targeting using nanocarriers is of increasing importance in the prophylaxis and treatment of dermatological or other diseases. For the first time, the present study demonstrated the photo-activated release of the model drug fluorescein isothiocyanate (FITC) from topically applied gold nanoparticle-doped bovine serum albumin (AuNPs-doped BSA) particles using water-filtered infrared A (IRA) radiation in the hair follicles of an ex vivo porcine skin model. The results demonstrate the feasibility of using wIRA radiation to induce release of encapsulated drugs for the targeting of follicular structures, and provide a new vision on the development of optically addressable delivery systems for controlled release of drugs in the skin and skin appendages, i.e. hair follicles and sebaceous glands. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Trps1 activates a network of secreted Wnt inhibitors and transcription factors crucial to vibrissa follicle morphogenesis

PubMed Central

Fantauzzo, Katherine A.; Christiano, Angela M.

2012-01-01

Mutations in TRPS1 cause trichorhinophalangeal syndrome types I and III, which are characterized by sparse scalp hair in addition to craniofacial and skeletal abnormalities. Trps1 is a vertebrate transcription factor that contains nine zinc-finger domains, including a GATA-type zinc finger through which it binds DNA. Mice in which the GATA domain of Trps1 has been deleted (Trps1Δgt/Δgt) have a reduced number of pelage follicles and lack vibrissae follicles postnatally. To identify the transcriptional targets of Trps1 in the developing vibrissa follicle, we performed microarray hybridization analysis, comparing expression patterns in the whisker pads of wild-type versus Trps1Δgt/Δgt embryos. We identified a number of transcription factors and Wnt inhibitors among transcripts downregulated in the mutant embryos and several extracellular matrix proteins that were upregulated in the mutant samples, and demonstrated that target gene expression levels were altered in vivo in Trps1Δgt/Δgt vibrissae. Unexpectedly, we discovered that Trps1 can directly bind the promoters of its target genes to activate transcription, expanding upon its established role as a transcriptional repressor. Our findings identify Trps1 as a novel regulator of the Wnt signaling pathway and of early hair follicle progenitors in the developing vibrissa follicle. PMID:22115758

The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration.

PubMed

Chen, Chih-Chiang; Plikus, Maksim V; Tang, Pin-Chi; Widelitz, Randall B; Chuong, Cheng Ming

2016-04-10

Hair and feathers are unique because (1) their stem cells are contained within a follicle structure, (2) they undergo cyclic regeneration repetitively throughout life, (3) regeneration occurs physiologically in healthy individuals and (4) regeneration is also induced in response to injury. Precise control of this cyclic regeneration process is essential for maintaining the homeostasis of living organisms. While stem cells are regulated by the intra-follicle-adjacent micro-environmental niche, this niche is also modulated dynamically by extra-follicular macro-environmental signals, allowing stem cells to adapt to a larger changing environment and physiological needs. Here we review several examples of macro-environments that communicate with the follicles: intradermal adipose tissue, innate immune system, sex hormones, aging, circadian rhythm and seasonal rhythms. Related diseases are also discussed. Unveiling the mechanisms of how stem cell niches are modulated provides clues for regenerative medicine. Given that stem cells are hard to manipulate, focusing translational therapeutic applications at the environments appears to be a more practical approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microbiology of folliculitis: a histological study of 39 cases.

PubMed

Jahns, Anika C; Lundskog, Bertil; Berg, Johanna; Jonsson, Rebecca; McDowell, Andrew; Patrick, Sheila; Golovleva, Irina; Palmer, Ruth H; Alexeyev, Oleg A

2014-01-01

Folliculitis is a common inflammatory skin syndrome. Several microbial organisms have been put forward as causative agents, but few studies visualized microbes directly in inflamed hair follicles. This retrospective study investigated bacterial and fungal colonization of inflamed hair follicles in patients with clinically diagnosed non-infectious folliculitis. Skin biopsies from 39 folliculitis patients and 27 controls were screened by fluorescence in situ hybridization (FISH) using broad-range bacterial and fungal probes and by immunofluorescence microscopy using a monoclonal antibody towards Gram-positive bacteria. Specific monoclonal and polyclonal antibodies towards Staphylococcus spp. and Propionibacterium acnes were applied for further species identification. Inflamed follicles were associated with bacterial colonization in 10 samples (26%) and fungal colonization in three samples (8%). Staphylococcus spp. were observed in inflamed follicles in seven samples (18%). Two samples were positive for P. acnes, which were identified as either type II or type IB/type III. Both Staphylococcus spp. and P. acnes were seen in macrocolonies/biofilm structures. In conclusion, one-third of patients with clinically diagnosed, non-infectious folliculitis exhibited microbial colonization with predominance of Staphylococcus spp. © 2013 APMIS Published by Blackwell Publishing Ltd.

The impact of body site, topical melatonin and brushing on hair regrowth after clipping normal Siberian Husky dogs.

PubMed

Diaz, Sandra F; Torres, Sheila M F; Nogueira, Sandra A F; Gilbert, Sophie; Jessen, Carl R

2006-02-01

The aims of this study were to determine the impact of body site, vigorous brushing and topical melatonin treatment on hair regrowth after clipping normal dogs. Siberian Husky dogs were randomly assigned to three groups of eight dogs each. All dogs had the lumbosacral region and both lateral thighs clipped. The left thigh and lumbosacral area received no treatment and were compared in all 24 dogs. Eight dogs had the right thigh treated with 0.1% melatonin twice daily for 2 months, and hair regrowth was compared with the left thigh. Eight dogs had the right thigh brushed twice daily for 2 months, and hair regrowth was compared with the left thigh. Eight dogs had neither thigh treated. Hairs were plucked before and 2 months postclipping, and the proportion of hair growth from the original length was calculated and compared as described above. Biopsy samples were collected before and after treatment to determine if brushing induced dermal inflammation and melatonin increased the proportion of anagen follicles. Proportionally, left thigh hairs were significantly longer compared to lumbosacral hairs 2 months postclipping. No significant differences in hair regrowth were noted between the nontreated thigh and the thigh treated with melatonin or brushed. No significant difference in dermal inflammation was noted before and after brushing. No significant differences were observed in the proportion of anagen follicles before and after topical melatonin treatment. Our results showed that the hairs in the lumbosacral region were proportionally shorter than lateral thigh hairs 2 months postclipping. Moreover, topical melatonin and brushing had no impact on hair regrowth after clipping normal dogs.

Contribution of hair density and hair diameter to the appearance and progression of androgenetic alopecia in Japanese men.

PubMed

Ishino, A; Takahashi, T; Suzuki, J; Nakazawa, Y; Iwabuchi, T; Tajima, M

2014-11-01

Androgenetic alopecia (AGA) is the most common type of baldness in men. The balding process is associated with the gradual miniaturization of hair follicles and successive hair loss. However, the relative contributions of hair density and diameter to AGA are still unclear. Hair density and hair diameter were investigated in Japanese men with or without AGA to elucidate the importance of these factors in the balding process. Male Japanese subjects with or without AGA (n = 369) were included in this study. Hair appearance at the vertex was evaluated by comparison with a series of standard photographs. Hair density was measured using a phototrichogram-based videomicroscopy technique, and hair diameter was assessed by comparison with a series of calibrated threads on the phototrichogram image. All subjects with AGA were ≥ 25 years of age. The mean percentage of thick hairs (> 80 μm) in all subjects with AGA was significantly lower than that in subjects without AGA aged ≥ 25 years (P < 0·01), but the mean percentage of vellus hairs (< 40 μm) in subjects with AGA was significantly higher (P < 0·001). By contrast, the mean density of the hair in all patients with AGA did not significantly differ from the density of those without AGA aged ≥ 25 years. However, the mean density of the hair in subjects without AGA aged < 25 years was significantly higher than that of both subjects without AGA aged ≥ 25 years (P < 0·001) and all subjects with AGA. Hair loss in men with AGA results mainly from the miniaturization of hair follicles rather than the loss of hair (shedding), at least for individuals who are ≥ 25 years of age and present with AGA. © 2014 British Association of Dermatologists.

Improvement of androgenetic alopecia with topical Sophora flavescens Aiton extract, and identification of the two active compounds in the extract that stimulate proliferation of human hair keratinocytes.

PubMed

Takahashi, T; Ishino, A; Arai, T; Hamada, C; Nakazawa, Y; Iwabuchi, T; Tajima, M

2016-04-01

Androgenetic alopecia (AGA) is a hair loss disorder that commonly affects middle-aged men. To date, the properties of a number of natural or synthetic substances have been investigated for their ability to improve the condition. To evaluate the hair growth-promoting activities of an extract from the root of Sophora flavescens Aiton. We used a human hair keratinocyte proliferation assay and ex vivo organ cultures of human hair follicle to examine the potential of the extract to stimulate hair growth via anagen elongation. We isolated the compounds promoting the growth of epithelial cells, and determined their chemical structures. A randomized, double-blinded, placebo-controlled clinical study for S. flavescens extract was carried out for 6 months with patients with AGA. The extract stimulated the proliferation of hair keratinocytes at a concentration of 0.1 ng/mL, while 100 ng/mL of the extract had a marked effect on hair shaft elongation in an organ culture of human hair follicle. Cell proliferation assay-directed fractionation led to the identification of two pterocarpan derivatives, L-maackiain and medicarpin, as active compounds that promote the proliferation of human hair keratinocytes. Studies in human subjects showed that improvement in the inspected alopecia scores in the lotion plus extract group were significant over a period of 6 months (P < 0.01). S. flavescens root extract is effective for the treatment of AGA. The isolated two pterocarpans might have important role in this effect. © 2015 British Association of Dermatologists.

Hair growth promoting activity of cedrol isolated from the leaves of Platycladus orientalis.

PubMed

Zhang, Yan; Han, Ling; Chen, Shan-Shan; Guan, Jian; Qu, Fan-Zhi; Zhao, Yu-Qing

2016-10-01

Platycladus orientalis (L.) Franco is traditionally known to potentiate hair growth promotion. However, there has been no report on its main active ingredient responsible for the hair growth activity. In the current work, cedrol as a major constituent from P. orientalis was evaluated for its potential on hair growth in vivo. Different concentrations of cedrol (10, 20 and 30mg/mL) were applied topically over the shaved skin of C57BL/6 mice and monitored for 21days. Results indicated that cedrol significantly promoted hair growth in a dose-dependent manner, particularly for the female mice. Both male and female mice groups treated with 30mg/mL cedrol required shorter time than the blank control and 2% minoxidil groups at different growth stages. Compared with the blank control (8.87mm) and 2% minoxidil (9.94mm) groups at 21days, the hair length of female mice treated with 30mg/mL cedrol showed a remarkable increase with the value of 11.07mm. Hair in male and female mice groups treated with 30mg/mL cedrol was heavier than the 2% minoxidil (38.2 and 35.9mg, respectively) groups with the weight of 42.6 and 45.2mg, respectively. Further observation of the hair follicle demonstrated that cedrol exerted a remarkable effect on the hair follicle length. These findings suggested that cedrol may be the main active ingredient of P. orientalis and have the potential of becoming a new hair growth promoter. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Induction of synapse associated protein 102 expression in cyclosporin A-stimulated hair growth.

PubMed

Kim, Chang Deok; Lee, Min-Ho; Sohn, Kyung-Cheol; Kim, Jin-Man; Li, Sheng Jin; Rang, Moon-Jeong; Roh, Seok-Seon; Oh, Young-Seon; Yoon, Tae-Jin; Im, Myung; Seo, Young-Joon; Lee, Jeung-Hoon; Park, Jang-Kyu

2008-08-01

Cyclosporin A (CsA) has been used as a potent immunosuppressive agent for inhibiting the graft rejection after organ transplantation. However, CsA provokes lots of side effects including hirsutism, the phenomenon of abnormal hair growth in the body. In the present study, we investigated the hair growth stimulating effect of CsA using in vivo and in vitro test models. When topically applied on the back skin of mice, CsA induced fast telogen to anagen transition. In contrast, CsA had no effect on the growth of human hair follicle tissues cultured in vitro, indicating that it might not have the mitogenic effect on hair follicles. To identify the genes related with CsA-induced hair growth, we performed differential display RT-PCR. Among the genes obtained, the expression of synapse associated protein 102 (SAP102) was verified using competitive RT-PCR. The result showed that the expression of SAP102 was significantly induced by CsA treatment in the back skin of C57BL/6 mice. However, the increase of SAP102 mRNA was also seen in spontaneous anagen mice, suggesting that induction of SAP102 is one event of the anagen hair growth response regardless of how the growth state was induced. SAP102 was not expressed in cultured human hair outer root sheath and dermal papilla cells. Immunohistochemistry analysis showed that CsA induced the expression of SAP102 in perifollicular region of mouse anagen hair. Together, these results suggest that SAP102 is one of hair-cycle-dependent genes, whose expression is related with the anagen progression.

Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells

PubMed Central

Veraitch, Ophelia; Mabuchi, Yo; Matsuzaki, Yumi; Sasaki, Takashi; Okuno, Hironobu; Tsukashima, Aki; Amagai, Masayuki; Okano, Hideyuki; Ohyama, Manabu

2017-01-01

The dermal papilla (DP) is a specialised mesenchymal component of the hair follicle (HF) that plays key roles in HF morphogenesis and regeneration. Current technical difficulties in preparing trichogenic human DP cells could be overcome by the use of highly proliferative and plastic human induced pluripotent stem cells (hiPSCs). In this study, hiPSCs were differentiated into induced mesenchymal cells (iMCs) with a bone marrow stromal cell phenotype. A highly proliferative and plastic LNGFR(+)THY-1(+) subset of iMCs was subsequently programmed using retinoic acid and DP cell activating culture medium to acquire DP properties. The resultant cells (induced DP-substituting cells [iDPSCs]) exhibited up-regulated DP markers, interacted with human keratinocytes to up-regulate HF related genes, and when co-grafted with human keratinocytes in vivo gave rise to fibre structures with a hair cuticle-like coat resembling the hair shaft, as confirmed by scanning electron microscope analysis. Furthermore, iDPSCs responded to the clinically used hair growth reagent, minoxidil sulfate, to up-regulate DP genes, further supporting that they were capable of, at least in part, reproducing DP properties. Thus, LNGFR(+)THY-1(+) iMCs may provide material for HF bioengineering and drug screening for hair diseases. PMID:28220862

BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties

PubMed Central

Rendl, Michael; Polak, Lisa; Fuchs, Elaine

2008-01-01

Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial–mesenchymal cross-talk necessary to make hair. PMID:18281466

Mutations in gasdermin 3 cause aberrant differentiation of the hair follicle and sebaceous gland.

PubMed

Lunny, Declan P; Weed, Erica; Nolan, Patrick M; Marquardt, Andreas; Augustin, Martin; Porter, Rebecca M

2005-03-01

Defolliculated (Dfl) is a spontaneous mouse mutant with a hair-loss phenotype that includes altered sebaceous gland differentiation, short hair shafts, aberrant catagen stage of the hair cycle, and eventual loss of the hair follicle. Recently a similar mutant, finnegan (Fgn), with an identical phenotype was discovered during a phenotypic screen for mutations induced by chemical mutagenesis. The gene underlying the phenotype of both finnegan and defolliculated has been mapped to chromosome 11 and here we show that both mice harbor mutations in gasdermin 3 (Gsdm3), a gene of unknown function. Gsdm3(Dfl) is a B2 insertion near the 3' splice site of exon 7 and Gsdm3(Fgn) is a point mutation T278P. To investigate the role of the gasdermin gene family an antiserum was raised to a peptide highly homologous to all three mouse gasdermins and human gasdermin. Immunohistochemical analysis revealed that gasdermins are expressed specifically in cells at advanced stages of differentiation in the upper epidermis, the differentiating inner root sheath and hair shaft and in the most mature sebocytes of the sebaceous gland and preputial, meibomium, ceruminous gland, and anal glands. This expression pattern suggests a role for gasdermins in differentiation of the epidermis and its appendages.

Mechanism of action of minoxidil in the treatment of androgenetic alopecia is likely mediated by mitochondrial adenosine triphosphate synthase-induced stem cell differentiation.

PubMed

Goren, A; Naccarato, T; Situm, M; Kovacevic, M; Lotti, T; McCoy, J

2017-01-01

Topical minoxidil is the only topical drug approved by the US Food and Drug Administration (FDA) for the treatment of androgenetic alopecia. However, the exact mechanism by which minoxidil stimulates anagen phase and promotes hair growth is not fully understood. In the late telegen phase of the hair follicle growth cycle, stem cells located in the bulge region differentiate and re-enter anagen phase, a period of growth lasting 2-6 years. In androgenetic alopecia, the anagen phase is shortened and a progressive miniaturization of hair follicles occurs, eventually leading to hair loss. Several studies have demonstrated that minoxidil increases the amount of intracellular Ca2+, which has been shown to up-regulate the enzyme adenosine triphosphate (ATP) synthase. A recent study demonstrated that ATP synthase, independent of its role in ATP synthesis, promotes stem cell differentiation. As such, we propose that minoxidil induced Ca2+ influx can increase stem cell differentiation and may be a key factor in the mechanism by which minoxidil facilitates hair growth. Based on our theory, we provide a roadmap for the development of a new class of drugs for the treatment of androgenetic alopecia.

Mutations in the Cholesterol Transporter Gene ABCA5 Are Associated with Excessive Hair Overgrowth

PubMed Central

DeStefano, Gina M.; Kurban, Mazen; Anyane-Yeboa, Kwame; Dall'Armi, Claudia; Di Paolo, Gilbert; Feenstra, Heather; Silverberg, Nanette; Rohena, Luis; López-Cepeda, Larissa D.; Jobanputra, Vaidehi; Fantauzzo, Katherine A.; Kiuru, Maija; Tadin-Strapps, Marija; Sobrino, Antonio; Vitebsky, Anna; Warburton, Dorothy; Levy, Brynn; Salas-Alanis, Julio C.; Christiano, Angela M.

2014-01-01

Inherited hypertrichoses are rare syndromes characterized by excessive hair growth that does not result from androgen stimulation, and are often associated with additional congenital abnormalities. In this study, we investigated the genetic defect in a case of autosomal recessive congenital generalized hypertrichosis terminalis (CGHT) (OMIM135400) using whole-exome sequencing. We identified a single base pair substitution in the 5′ donor splice site of intron 32 in the ABC lipid transporter gene ABCA5 that leads to aberrant splicing of the transcript and a decrease in protein levels throughout patient hair follicles. The homozygous recessive disruption of ABCA5 leads to reduced lysosome function, which results in an accumulation of autophagosomes, autophagosomal cargos as well as increased endolysosomal cholesterol in CGHT keratinocytes. In an unrelated sporadic case of CGHT, we identified a 1.3 Mb cryptic deletion of chr17q24.2-q24.3 encompassing ABCA5 and found that ABCA5 levels are dramatically reduced throughout patient hair follicles. Collectively, our findings support ABCA5 as a gene underlying the CGHT phenotype and suggest a novel, previously unrecognized role for this gene in regulating hair growth. PMID:24831815

Role of thymosin beta 4 in hair growth.

PubMed

Gao, Xiao-Yu; Hou, Fang; Zhang, Zhi-Peng; Nuo, Ming-Tu; Liang, Hao; Cang, Ming; Wang, Zhi-Gang; Wang, Xin; Xu, Teng; Yan, Le-Yan; Guo, Xu-Dong; Liu, Dong-Jun

2016-08-01

Although thymosin beta 4 (Tβ4) is known to play a role in hair growth, its mechanism of action is unclear. We examined the levels of key genes in a Tβ4 epidermal-specific over-expressing mouse model and Tβ4 global knockout mouse model to explore how Tβ4 affects hair growth. By depilation and histological examination of the skin, we confirmed the effect of Tβ4 on hair growth, the number of hair shafts and hair follicle (HF) structure. The mRNA and protein expression of several genes involved in hair growth were detected by real-time PCR and western blotting, respectively. Changes in the expression of β-catenin and Lef-1, the two key molecules in the Wnt signaling pathway, were similar to the changes observed in Tβ4 expression. We also found that compared to the control mice, the mRNA and protein expression of MMP-2 and VEGF were increased in the Tβ4 over-expressing mice, while the level of E-cadherin (E-cad) remained the same. Further, in the Tβ4 global knockout mice, the mRNA and protein levels of MMP-2 and VEGF decreased dramatically and the level of E-cad was stable. Based on the above results, we believe that Tβ4 may regulate the levels of VEGF and MMP-2 via the Wnt/β-catenin/Lef-1 signaling pathway to influence the growth of blood vessels around HFs and to activate cell migration. Tβ4 may have potential for the treatment of hair growth problems in adults, and its effects should be further confirmed in future studies.

Canine noninflammatory alopecia: a comprehensive evaluation of common and distinguishing histological characteristics.

PubMed

Müntener, Tabitha; Schuepbach-Regula, Gertraud; Frank, Linda; Rüfenacht, Silvia; Welle, Monika M

2012-06-01

Noninflammatory alopecia is a frequent problem in dogs, and the pathogenesis is still unclear. The objective of this study was a comparative histological description of skin biopsies from dogs with different alopecic disorders and control dogs matched for coat type, season and disease duration. Twenty-one cases of alopecia X in plush-coated dogs, 12 cases of recurrent flank alopecia, three cases of hyperestrogenism, 15 cases of hyperadrenocorticism, 12 cases of hypothyroidism and 12 cases of primary alopecic disorders of unknown cause were evaluated. The controls were biopsies from 38 dogs of different coat types. We evaluated five serial sections of each biopsy histologically and immunohistologically to compare the histological findings within the disease groups and with the control. All the dogs with hair cycle disorders had a significant increase in the number of hairless hair follicles, which we assigned to kenogen. In addition, dogs with alopecia X had the lowest percentage of anagen follicles and the highest percentage of telogen follicles. The marked increase in kenogen follicles is a strong indication that the induction of the new anagen phase is impaired in hair cycle disorders. The findings in dogs with alopecia X further suggest that premature catagen is also involved in the pathogenesis. Further work to investigate the stem cell compartment and possible initiating factors for the different cycle phases is required to elucidate the exact pathogenesis. © 2012 The Authors. Veterinary Dermatology. © 2012 ESVD and ACVD.

E- and P-cadherin expression during murine hair follicle morphogenesis and cycling.

PubMed

Müller-Röver, S; Tokura, Y; Welker, P; Furukawa, F; Wakita, H; Takigawa, M; Paus, R

1999-08-01

The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR. The expression of both cadherins was strikingly hair cycle-dependent and restricted to distinct anatomical HF compartments. During HF morphogenesis, hair bud keratinocytes displayed strong Ecad and Pcad immunoreactivity (IR). While neonatal epidermis showed Ecad IR in all epidermal layers, Pcad IR was restricted to the basal layer. During later stages of HF morphogenesis and during anagen IV-VI of the adolescent murine hair cycle, the outer root sheath showed strong E- and Pcad IR. Instead, the outermost portion of the hair matrix and the inner root sheath displayed isolated Ecad IR, while the innermost portion of the hair matrix exhibited isolated Pcad IR. During telogen, all epidermal and follicular keratinocytes showed strong Ecad IR. This is in contrast to Pcad, whose IR was stringently restricted to matrix and secondary hair germ keratinocytes which are in closest proximity to the dermal papilla. These findings suggest that isolated or combined E- and/or Pcad expression is involved in follicular pattern formation by segregating HF keratinocytes into functionally distinct subpopulations; most notably, isolated Pcad expression may segregate those hair matrix keratinocytes into one functional epithelial tissue unit, which is particularly susceptible to growth control by dermal papilla-derived morphogens. The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders.

Hair follicle is a target of stress hormone and autoimmune reactions.

PubMed

Ito, Taisuke

2010-11-01

Interest in the hair follicle (HF) has recently increased, yet the detailed mechanisms of HF function and immune privilege (IP) have not yet been elucidated. This review discusses the critical points of immunobiology and hormonal aspects of HFs. The HF is a unique mini-organ because it has its own immune system and hormonal milieu. In addition, the HF immune and hormonal systems may greatly affect skin immunobiology. Therefore, knowledge of HF immunobiology and hormonal aspects will lead to a better understanding of skin biology. The HF has a unique hair cycle (anagen, catagen and telogen) and contains stem cells in the bulge area. The HF is closely related to sebaceous glands and the nervous system. This article reviews the interaction between the endocrine/immune system and HFs, including the pathogenesis of alopecia areata associated with stress. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Abnormalities of hair structure and skin histology derived from CRISPR/Cas9-based knockout of phospholipase C-delta 1 in mice.

PubMed

Liu, Yu-Min; Liu, Wei; Jia, Jun-Shuang; Chen, Bang-Zhu; Chen, Heng-Wei; Liu, Yu; Bie, Ya-Nan; Gu, Peng; Sun, Yan; Xiao, Dong; Gu, Wei-Wang

2018-05-25

Hairless mice have been widely applied in skin-related researches, while hairless pigs will be an ideal model for skin-related study and other biomedical researches because of the similarity of skin structure with humans. The previous study revealed that hairlessness phenotype in nude mice is caused by insufficient expression of phospholipase C-delta 1 (PLCD1), an essential molecule downstream of Foxn1, which encouraged us to generate PLCD1-deficient pigs. In this study, we plan to firstly produce PLCD1 knockout (KO) mice by CRISPR/Cas9 technology, which will lay a solid foundation for the generation of hairless PLCD1 KO pigs. Generation of PLCD1 sgRNAs and Cas 9 mRNA was performed as described (Shao in Nat Protoc 9:2493-2512, 2014). PLCD1-modified mice (F0) were generated via co-microinjection of PLCD1-sgRNA and Cas9 mRNA into the cytoplasm of C57BL/6J zygotes. Homozygous PLCD1-deficient mice (F1) were obtained by intercrossing of F0 mice with the similar mutation. PLCD1-modified mice (F0) showed progressive hair loss after birth and the genotype of CRISPR/Cas9-induced mutations in exon 2 of PLCD1 locus, suggesting the sgRNA is effective to cause mutations that lead to hair growth defect. Homozygous PLCD1-deficient mice (F1) displayed baldness in abdomen and hair sparse in dorsa. Histological abnormalities of the reduced number of hair follicles, irregularly arranged and curved hair follicles, epidermal hyperplasia and disturbed differentiation of epidermis were observed in the PLCD1-deficient mice. Moreover, the expression level of PLCD1 was significantly decreased, while the expression levels of other genes (i.e., Krt1, Krt5, Krt13, loricrin and involucrin) involved in the differentiation of hair follicle were remarkerably increased in skin tissues of PLCD1-deficient mice. In conclusion, we achieve PLCD1 KO mice by CRISPR/Cas9 technology, which provide a new animal model for hair development research, although homozygotes don't display completely hairless phenotype as expected.

Hair-Growth-Promoting Effect of Conditioned Medium of High Integrin α6 and Low CD 71 (α6bri/CD71dim) Positive Keratinocyte Cells

PubMed Central

Won, Chong Hyun; Jeong, Yun-Mi; Kang, Sangjin; Koo, Tae-Sung; Park, So-Hyun; Park, Ki-Young; Sung, Young-Kwan; Sung, Jong-Hyuk

2015-01-01

Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor). A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells. PMID:25706512

Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re‐epithelialization

PubMed Central

Garcin, Clare L.; Ansell, David M.; Headon, Denis J.; Paus, Ralf

2016-01-01

Abstract The cutaneous healing response has evolved to occur rapidly, in order to minimize infection and to re‐establish epithelial homeostasis. Rapid healing is achieved through complex coordination of multiple cell types, which importantly includes specific cell populations within the hair follicle (HF). Under physiological conditions, the epithelial compartments of HF and interfollicular epidermis remain discrete, with K15+ve bulge stem cells contributing progeny for HF reconstruction during the hair cycle and as a basis for hair shaft production during anagen. Only upon wounding do HF cells migrate from the follicle to contribute to the neo‐epidermis. However, the identity of the first‐responding cells, and in particular whether this process involves a direct contribution of K15+ve bulge cells to the early stage of epidermal wound repair remains unclear. Here we demonstrate that epidermal injury in murine skin does not induce bulge activation during early epidermal wound repair. Specifically, bulge cells of uninjured HFs neither proliferate nor appear to migrate out of the bulge niche upon epidermal wounding. In support of these observations, Diphtheria toxin‐mediated partial ablation of K15+ve bulge cells fails to delay wound healing. Our data suggest that bulge cells only respond to epidermal wounding during later stages of repair. We discuss that this response may have evolved as a protective safeguarding mechanism against bulge stem cell exhaust and tumorigenesis. Stem Cells 2016;34:1377–1385 PMID:26756547

β-Catenin-Dependent and -Independent Effects of ΔN-Plakoglobin on Epidermal Growth and Differentiation

PubMed Central

Teulière, J.; Faraldo, M. M.; Shtutman, M.; Birchmeier, W.; Huelsken, J.; Thiery, J. P.; Glukhova, M. A.

2004-01-01

Both β-catenin and plakoglobin can stimulate the expression of Lef/Tcf target genes in vitro. β-Catenin is known to associate with Lef/Tcf factors and to participate directly in transactivation in vivo, whereas the role of plakoglobin in transcriptional regulation has been less studied. To analyze the functions of plakoglobin in vivo, we generated transgenic mice expressing in the epidermis N-terminally truncated plakoglobin (ΔN122-PG) lacking the glycogen synthase kinase 3β phosphorylation sites and therefore protected against degradation (transgenic line K5-ΔN122-PG). The expression of ΔN122-PG led to the formation of additional hair germs, hyperplastic hair follicles, and noninvasive hair follicle tumors, a phenotype reminiscent of that induced by expression of N-terminally truncated β-catenin. However, if expressed in β-catenin-null epidermis, ΔN122-PG did not induce new hair follicle germs and follicular tumors. Thus, ΔN122-PG cannot substitute for β-catenin in its signaling functions in vivo and the phenotype observed in K5-ΔN122-PG mouse skin must be due to the aberrant activation of β-catenin signaling. On the other hand, the expression of ΔN122-PG in β-catenin-null skin significantly increased the survival rate of mutant mice, rescued differentiation, and limited excessive proliferation in the interfollicular epidermis, suggesting that plakoglobin may be involved in the intracellular signaling events essential for epidermal differentiation. PMID:15367683

Use PCR and a Single Hair To Produce a "DNA Fingerprint."

ERIC Educational Resources Information Center

Campbell, A. Malcolm; And Others

1997-01-01

Presents a laboratory procedure that involves students extracting their own DNA from a single hair follicle, using the polymerase chain reaction (PCR) to amplify a polymorphic locus, performing electrophoresis on the PCR products on an agarose gel, and visualizing the alleles to generate a "DNA fingerprint." Discusses theoretical background,…

Histologic features of alopecias: part II: scarring alopecias.

PubMed

Bernárdez, C; Molina-Ruiz, A M; Requena, L

2015-05-01

The diagnosis of disorders of the hair and scalp can generally be made on clinical grounds, but clinical signs are not always diagnostic and in some cases more invasive techniques, such as a biopsy, may be necessary. This 2-part article is a detailed review of the histologic features of the main types of alopecia based on the traditional classification of these disorders into 2 major groups: scarring and nonscarring alopecias. Scarring alopecias are disorders in which the hair follicle is replaced by fibrous scar tissue, a process that leads to permanent hair loss. In nonscarring alopecias, the follicles are preserved and hair growth can resume when the cause of the problem is eliminated. In the second part of this review, we describe the histologic features of the main forms of scarring alopecia. Since a close clinical-pathological correlation is essential for making a correct histopathologic diagnosis of alopecia, we also include a brief description of the clinical features of the principal forms of this disorder. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway

PubMed Central

Ahmed, Mohammed I.; Alam, Majid; Emelianov, Vladimir U.; Poterlowicz, Krzysztof; Patel, Ankit; Sharov, Andrey A.; Mardaryev, Andrei N.

2014-01-01

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging. PMID:25422376

Histologic features of alopecias-part I: nonscarring alopecias.

PubMed

Bernárdez, C; Molina-Ruiz, A M; Requena, L

2015-04-01

The diagnosis of disorders of the hair and scalp can generally be made on clinical grounds, but clinical signs are not always diagnostic and in some cases more invasive techniques, such as a biopsy, may be necessary. This 2-part article is a detailed review of the histologic features of the main types of alopecia based on the traditional classification of these disorders into 2 major groups: scarring and nonscarring alopecias. Scarring alopecias are disorders in which the hair follicle is replaced by fibrous scar tissue, a process that leads to permanent hair loss. In nonscarring alopecias, the follicles are preserved and hair growth can resume when the cause of the problem is eliminated. In the first part of this review, we describe the histologic features of the main forms of nonscarring alopecia. Since a close clinical-pathological correlation is essential for making a correct histologic diagnosis of alopecia, we also include a brief description of the clinical features of the principal forms of this disorder. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Enhancing hair growth in male androgenetic alopecia by a combination of fractional CO2 laser therapy and hair growth factors.

PubMed

Huang, Yue; Zhuo, Fenglin; Li, Linfeng

2017-11-01

Laser therapy and growth factors have been used as alternative treatments for male androgenetic alopecia (MAA). The aim of this study is to determine the efficacy and safety of hair growth factors alone or combined with ablative carbon dioxide (CO 2 ) fractional laser therapy in MAA. Twenty-eight men were enrolled in this randomized half-split study based on a left-head to right-head pattern. Fractional CO 2 laser treatment was unilaterally performed; hair growth factors were bilaterally applied. Six sessions with 2-week intervals were performed. Global photographs and dermoscopy assessments were performed at the baseline and 4 months after first treatment. Global photographs underwent blinded review by three independent dermatologists. Scanning electron microscopy was used to compare changes in hair-follicle phase and hair-shaft diameter. Twenty-seven participants completed the 4-month treatment schedule. One patient was lost. Mean hair density increased from 114 ± 27 to 143 ± 25/cm 2 (P < 0.001) in the combined group and from 113 ± 24 to 134 ± 19/cm 2 in the growth factor group (P < 0.001). The mean change from baseline between two groups was also compared (P = 0.003). Global photographs showed improvement in 93% (25/27) patients in the combined group and 67% (18/27) patients in the growth factor group. Under scanning electron microscopy, hair follicles appeared to transition from telogen to anagen, and hair-shaft diameter increased in five randomly selected patients. Ablative fractional CO 2 laser combined with hair growth factors may serve as an alternative treatment for MAA in individuals unwilling/unable to undergo medical or surgical treatment.

Hair cycle control by leptin as a new anagen inducer.

PubMed

Sumikawa, Yasuyuki; Inui, Shigeki; Nakajima, Takeshi; Itami, Satoshi

2014-01-01

Our purpose is to clarify the physiological role of leptin in hair cycle as leptin reportedly causes activation of Stat3, which is indispensable for hair cycling. While hair follicles in dorsal skin of 5-week-old C57/BL6 mice had progressed to late anagen phase, those in dorsal skin of 5-week-old leptin receptor deficient db/db mice remained in the first telogen and later entered the anagen at postnatal day 40, indicating that deficiency in leptin receptor signalling delayed the second hair cycle progression. Next, we shaved dorsal hairs on wild-type mice at postnatal 7 weeks and injected skin with mouse leptin or a mock. After 20 days, although mock injection showed no effect, hair growth occurred around leptin injection area. Human leptin fragment (aa22-56) had similar effects. Although the hair cycle of ob/ob mice was similar to that of wild-type mice, injection of mouse leptin on ob/ob mice at postnatal 7 weeks induced anagen transition. Immunohistochemically, leptin is expressed in hair follicles from catagen to early anagen in wild-type mice, suggesting that leptin is an anagen inducer in vivo. Phosphorylation of Erk, Jak2 and Stat3 in human keratinocytes was stimulated by leptin and leptin fragment. In addition, RT-PCR and ELISA showed that the production of leptin by human dermal papilla cells increased under hypoxic condition, suggesting that hypoxia in catagen/telogen phase promotes leptin production, preparing for entry into the next anagen. In conclusion, leptin, a well-known adipokine, acts as an anagen inducer and represents a new player in hair biology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Discovery of cashmere goat (Capra hircus) microRNAs in skin and hair follicles by Solexa sequencing.

PubMed

Yuan, Chao; Wang, Xiaolong; Geng, Rongqing; He, Xiaolin; Qu, Lei; Chen, Yulin

2013-07-28

MicroRNAs (miRNAs) are a large family of endogenous, non-coding RNAs, about 22 nucleotides long, which regulate gene expression through sequence-specific base pairing with target mRNAs. Extensive studies have shown that miRNA expression in the skin changes remarkably during distinct stages of the hair cycle in humans, mice, goats and sheep. In this study, the skin tissues were harvested from the three stages of hair follicle cycling (anagen, catagen and telogen) in a fibre-producing goat breed. In total, 63,109,004 raw reads were obtained by Solexa sequencing and 61,125,752 clean reads remained for the small RNA digitalisation analysis. This resulted in the identification of 399 conserved miRNAs; among these, 326 miRNAs were expressed in all three follicular cycling stages, whereas 3, 12 and 11 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. We also identified 172 potential novel miRNAs by Mireap, 36 miRNAs were expressed in all three cycling stages, whereas 23, 29 and 44 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. The expression level of five arbitrarily selected miRNAs was analyzed by quantitative PCR, and the results indicated that the expression patterns were consistent with the Solexa sequencing results. Gene Ontology and KEGG pathway analyses indicated that five major biological pathways (Metabolic pathways, Pathways in cancer, MAPK signalling pathway, Endocytosis and Focal adhesion) accounted for 23.08% of target genes among 278 biological functions, indicating that these pathways are likely to play significant roles during hair cycling. During all hair cycle stages of cashmere goats, a large number of conserved and novel miRNAs were identified through a high-throughput sequencing approach. This study enriches the Capra hircus miRNA databases and provides a comprehensive miRNA transcriptome profile in the skin of goats during the hair follicle cycle.

Expression characteristics of BMP2, BMPR-IA and Noggin in different stages of hair follicle in yak skin.

PubMed

Song, Liang-Li; Cui, Yan; Yu, Si-Jiu; Liu, Peng-Gang; Liu, Jun; Yang, Xue; He, Jun-Feng; Zhang, Qian

2018-05-01

Bone morphogenetic protein 2 (BMP2), BMP receptor-IA (BMPR-IA), and the BMP2 antagonist Noggin are important proteins involved in regulating the hair follicle (HF) cycle in skin. In order to explore the expression profiles of BMP2, BMPR-IA, and Noggin in the HF cycle of yak skin, we collected adult yak skin in the telogen, proanagen, and midanagen phases of HFs and evaluated gene and protein expression by real-time quantitative polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. qRT-PCR and western blotting results showed that BMP2 and BMPR-IA expression levels were highest in the telogen of HFs and higher than that of Noggin in the same phase. The expression of Noggin was significantly higher in proanagen and midanagen phases of HFs than in the telogen phase, with the highest expression observed in the proanagen phase. Moreover, the expression of Noggin in the proanagen phase was significantly higher than those of BMP2 and BMPR-IA during the same phase. Immunohistochemistry results showed that BMP2, BMPR-IA, and Noggin were expressed in the skin epidermis, sweat glands, sebaceous glands, HF outer root sheath, and hair matrix. In summary, the characteristic expression profiles of BMP2, BMPR-IA, and Noggin suggested that BMP2 and BMPR-IA had inhibitory effects on the growth of HFs in yaks, whereas Noggin promoted the growth of yak HFs, mainly by affecting skin epithelial cell activity. These results provide a basis for further studies of HF development and cycle transition in yak skin. Copyright © 2017. Published by Elsevier Inc.

Protease activity, localization and inhibition in the human hair follicle.

PubMed

Bhogal, R K; Mouser, P E; Higgins, C A; Turner, G A

2014-02-01

In humans, the process of hair shedding, referred to as exogen, is believed to occur independently of the other hair cycle phases. Although the actual mechanisms involved in hair shedding are not fully known, it has been hypothesized that the processes leading to the final step of hair shedding may be driven by proteases and/or protease inhibitor activity. In this study, we investigated the presence of proteases and protease activity in naturally shed human hairs and assessed enzyme inhibition activity of test materials. We measured enzyme activity using a fluorescence-based assay and protein localization by indirect immunohistochemistry (IHC). We also developed an ex vivo skin model for measuring the force required to pull hair fibres from skin. Our data demonstrate the presence of protease activity in the tissue material surrounding club roots. We also demonstrated the localization of specific serine protease protein expression in human hair follicle by IHC. These data provide evidence demonstrating the presence of proteases around the hair club roots, which may play a role during exogen. We further tested the hypothesis that a novel protease inhibitor system (combination of Trichogen) and climbazole) could inhibit protease activity in hair fibre club root extracts collected from a range of ethnic groups (U.K., Brazil, China, first-generation Mexicans in the U.S.A., Thailand and Turkey) in both males and females. Furthermore, we demonstrated that this combination is capable of increasing the force required to remove hair in an ex vivo skin model system. These studies indicate the presence of proteolytic activity in the tissue surrounding the human hair club root and show that it is possible to inhibit this activity with a combination of Trichogen and climbazole. This technology may have potential to reduce excessive hair shedding. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Nestin is expressed in HMB-45 negative melanoma cells in dermal parts of nodular melanoma.

PubMed

Kanoh, Maho; Amoh, Yasuyuki; Tanabe, Kenichi; Maejima, Hideki; Takasu, Hiroshi; Katsuoka, Kensei

2010-06-01

Nestin, a marker of neural stem cells, is expressed in the stem cells of the mouse hair follicle. The nestin-expressing hair follicle stem cells can differentiate into neurons, glia, keratocytes, smooth muscle cells and melanocytes in vitro. These pluripotent nestin-expressing stem cells are keratin 15 (K15)-negative, suggesting that they are in a relatively undifferentiated state. Recent studies suggest that the epithelial stem cells are important in tumorigenesis, and nestin expression is thought to be important in tumorigenesis. In the present study, we examined the expression of the hair follicle and neural stem cell marker nestin, as well as S-100 and HMB-45, in melanoma. Nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in all five cases of amelanotic nodular melanomas. Moreover, nestin immunoreactivity was observed in the dermal parts in seven of 10 cases of melanotic nodular melanomas. Especially, nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in the dermal parts of all 10 cases of HMB-45-negative amelanotic and melanotic nodular melanomas. On the other hand, nestin expression was negative in 10 of 12 cases of superficial spreading melanoma. These results suggest that nestin is an important marker of HMB-45-negative melanoma cells in the dermal parts of patients with nodular melanoma.

Temperature-Enhanced Follicular Penetration of Thermoresponsive Nanogels

NASA Astrophysics Data System (ADS)

Jung, Sora; Nagel, Gregor; Giulbudagian, Michael; Calderón, Marcelo; Patzelt, Alexa; Knorr, Fanny; Lademann, Jürgen

2018-05-01

Hair follicles can serve as an effective reservoir for dermal drug delivery upon the topical application of particulate substances. Here, the follicular penetration of an indodicarbocyanine-labelled thermoresponsive nanogel (189 nm) having a cloud point temperature of 34°C and linked via an acid-labile linker to the model drug indocarbocyanine was investigated. In total, 227 hair follicles of porcine ear skin were examined after topical application of the thermoresponsive nanogels at room temperature (21°C), physiological skin surface temperature (32°C) and core body temperature (37°C) for the follicular penetration depths of indodicarbocyanine and indocarbocyanine using confocal laser scanning microscopy. The results showed a significantly increased mean follicular penetration of the carrier to a depth of 298.8±85.8 μm after incubation at 37°C compared to samples incubated at 21°C and 32°C with mean follicular penetration depths of 202.7±81.7 μm and 219.4±52.9 μm, respectively (p<0.001). Possibly structural changes in the thermoresponsive nanogel induced by the increased incubation temperature led to an enhancement of follicular penetration. Therefore, thermoresponsive nanogels may be suitable for the temperature-enhanced penetration into the hair follicles under physiological conditions.

Pigmented Epithelioid Melanocytoma (PEM)/Animal Type Melanoma (ATM): Quest for an Origin. Report of One Unusual Case Indicating Follicular Origin and Another Arising in an Intradermal Nevus.

PubMed

Tarasen, Ashley; Carlson, J Andrew; Leonard, M Kathryn; Merlino, Glenn; Kaetzel, David; Slominski, Andrzej T

2017-08-15

Pigmented epithelioid melanocytoma (PEM) is a tumor encompassing epithelioid blue nevus of Carney complex (EBN of CNC) and was previously termed animal-type melanoma. Histologically PEMs are heavily pigmented spindled and epithelioid dermal melanocytic tumors with infiltrative borders, however, their origin remains unclear. Stem cells for the epidermis and hair follicle are located in the bulge area of the hair follicle with the potential to differentiate into multiple lineages. Multiple cutaneous carcinomas, including follicular cutaneous squamous cell carcinoma (FSCC), are thought to arise from stem cells in the follicular bulge. We present two cases of PEM/ATM in a 63 year-old male on the scalp with follicular origin and a 72 year-old female on the upper back arising in an intradermal nevus. Biopsy of both cases revealed a proliferation of heavily pigmented dermal nests of melanocytes with atypia. The Case 1 tumor was in continuation with the outer root sheath of the hair follicle in the bulge region. Case 2 arose in an intradermal melanocytic nevus. Rare mitotic figures, including atypical mitotic figures, were identified in both cases. We present two cases of PEM, with histologic evidence suggesting two origins: one from the follicular bulb and one from an intradermal nevus.

Gradient-dependent release of the model drug TRITC-dextran from FITC-labeled BSA hydrogel nanocarriers in the hair follicles of porcine ear skin.

PubMed

Tran, Ngo Bich Nga Nathalie; Knorr, Fanny; Mak, Wing Cheung; Cheung, Kwan Yee; Richter, Heike; Meinke, Martina; Lademann, Jürgen; Patzelt, Alexa

2017-07-01

Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

Persistent Pemphigus Vulgaris Showing Features of Tufted Hair Folliculitis

PubMed Central

Ko, Dong Kyun; Chae, In Soo; Chung, Ki Hun; Chung, Hyun

2011-01-01

Pemphigus vulgaris is an autoimmune blistering disease that commonly involves the scalp. Lesions of pemphigus vulgaris that persist on the scalp for a long period may be accompanied by tufted hair folliculitis. Only two previous accounts of tufted hair folliculitis developing in a lesion of pemphigus vulgaris have been reported. We report a 51-year-old-man with erosions and clusters of hair on the scalp. The scalp lesion had persisted for about 20 years. A histopathological examination of the skin lesion on the scalp revealed separation of the epidermis and clusters of several adjacent hair follicles. The patient was diagnosed with persistent pemphigus vulgaris of the scalp showing features of tufted hair folliculitis. PMID:22148026

Immunofluorescence findings in rapid whitening of scalp hair.

PubMed

Guin, J D; Kumar, V; Petersen, B H

1981-09-01

Rapid whitening of scalp hair developed during a three-month period along with a diffuse, subtotal alopecia in a patient. Immunofluorescence microscopy of biopsy material showed prominent deposits of IgG and IgM in a granular pattern in the epithelium of the lower portions of hair follicles. Some return of the color and amount of scalp hair occurred within a year, but occasional bouts of hair loss continued to occur. It is theorized that the rapid graying was caused by a selective loss of pigmented hair, which was perhaps caused by an immunologic mechanism. Some of the findings suggest that the cause of this patient's loss of hair color may be different from those of patients who have been previously described as having rapid whitening of scalp hair because of alopecia areata or vitiligo.

Personal samplers of bioavailable pesticides integrated with a hair follicle assay of DNA damage to assess environmental exposures and their associated risks in children.

PubMed

Vidi, Pierre-Alexandre; Anderson, Kim A; Chen, Haiying; Anderson, Rebecca; Salvador-Moreno, Naike; Mora, Dana C; Poutasse, Carolyn; Laurienti, Paul J; Daniel, Stephanie S; Arcury, Thomas A

2017-10-01

Agriculture in the United States employs youth ages ten and older in work environments with high pesticide levels. Younger children in rural areas may also be affected by indirect pesticide exposures. The long-term effects of pesticides on health and development are difficult to assess and poorly understood. Yet, epidemiologic studies suggest associations with cancer as well as cognitive deficits. We report a practical and cost-effective approach to assess environmental pesticide exposures and their biological consequences in children. Our approach combines silicone wristband personal samplers and DNA damage quantification from hair follicles, and was tested as part of a community-based participatory research (CBPR) project involving ten Latino children from farmworker households in North Carolina. Our study documents high acceptance among Latino children and their caregivers of these noninvasive sampling methods. The personal samplers detected organophosphates, organochlorines, and pyrethroids in the majority of the participants (70%, 90%, 80%, respectively). Pesticides were detected in all participant samplers, with an average of 6.2±2.4 detections/participant sampler. DNA damage in epithelial cells from the sheath and bulb of plucked hairs follicles was quantified by immunostaining 53BP1-labled DNA repair foci. This method is sensitive, as shown by dose response analyses to γ radiations where the lowest dose tested (0.1Gy) led to significant increased 53BP1 foci density. Immunolabeling of DNA repair foci has significant advantages over the comet assay in that specific regions of the follicles can be analyzed. In this cohort of child participants, significant association was found between the number of pesticide detections and DNA damage in the papilla region of the hairs. We anticipate that this monitoring approach of bioavailable pesticides and genotoxicity will enhance our knowledge of the biological effects of pesticides to guide education programs and safety policies. Copyright © 2017 Elsevier B.V. All rights reserved.

Serotonergic transmission at Merkel discs: modulation by exogenously applied chemical messengers and involvement of Ih currents.

PubMed

Chang, Weipang; Kanda, Hirosato; Ikeda, Ryo; Ling, Jennifer; Gu, Jianguo G

2017-05-01

The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In this study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers. We found that SA1 responses were potentiated by serotonin at low concentration (10 μM) but almost completely occluded by serotonin at high concentration (2 mM). In contrast, SA1 responses were not significantly affected by ATP and its metabolically stable analog α,β-methylene-ATP, glutamate, γ-aminobutyric acid (GABA), and histamine. SA1 responses were also not affected by antagonists for P2X receptors, ionotropic glutamate receptors, and ionotropic GABA and glycine receptors. Whole-cell patch-clamp recordings reconfirm the presence of both ionotropic and metabotropic 5-HT receptors on afferent neurons and their terminals innervating whisker hair follicles. All whisker afferent neurons expressed hyperpolarization-activated inward currents (I h ), which are potentiated by serotonin through the activation of metabotropic 5-HT receptors. Taken together, the findings substantiate the serotonergic mechanism of tactile transmission at Merkel discs and identify the involvement of I h currents in postsynaptic excitatory actions of serotonin. In addition, the findings do not favor any significant involvement of ATP, glutamate, histamine, GABA, or glycine in tactile transmission at the Merkel discs of whisker hair follicles. © 2017 International Society for Neurochemistry.

Dihydrotestosterone inhibits hair growth in mice by inhibiting insulin-like growth factor-I production in dermal papillae.

PubMed

Zhao, Juan; Harada, Naoaki; Okajima, Kenji

2011-10-01

We demonstrated that insulin-like growth factor-I (IGF-I) production in dermal papillae was increased and hair growth was promoted after sensory neuron stimulation in mice. Although the androgen metabolite dihydrotestosterone (DHT) inhibits hair growth by negatively modulating growth-regulatory effects of dermal papillae, relationship between androgen metabolism and IGF-I production in dermal papillae is not fully understood. We examined whether DHT inhibits IGF-I production by inhibiting sensory neuron stimulation, thereby preventing hair growth in mice. Effect of DHT on sensory neuron stimulation was examined using cultured dorsal root ganglion (DRG) neurons isolated from mice. DHT inhibits calcitonin gene-related peptide (CGRP) release from cultured DRG neurons. The non-steroidal androgen-receptor antagonist flutamide reversed DHT-induced inhibition of CGRP release. Dermal levels of IGF-I and IGF-I mRNA, and the number of IGF-I-positive fibroblasts around hair follicles were increased at 6h after CGRP administration. DHT administration for 3weeks decreased dermal levels of CGRP, IGF-I, and IGF-I mRNA in mice. Immunohistochemical expression of IGF-I and the number of proliferating cells in hair follicles were decreased and hair re-growth was inhibited in animals administered DHT. Co-administration of flutamide and CGRP reversed these changes induced by DHT administration. These observations suggest that DHT may decrease IGF-I production in dermal papillae by inhibiting sensory neuron stimulation through interaction with the androgen receptor, thereby inhibiting hair growth in mice. Copyright © 2011 Elsevier Ltd. All rights reserved.

Static and dynamic modes of 810 nm diode laser hair removal compared: A clinical and histological study

PubMed Central

2017-01-01

Background and Aims Laser hair removal has recently become a major indication. Diode lasers have become commercially available offering two modes of application: a stamping or static mode, and a dynamic mode whereby the handpiece is continuously moved across the target tissue. The present study was designed to compare the efficacy of these two approaches clinically and histologically. Subjects and Methods Twenty-five subjects participated in the study, 12 males and 13 females, ages ranging from 20 to 57 yr (Mean age 41.6 yr). A baseline hair count was performed on both the target areas. The ms-pulsed diode laser delivered 810 nm via a handpiece with a cooled tip, offering both static and dynamic modes which were used on the subjects' left and right crura, respectively. Pain during treatment was assessed using a visual analog scale (VAS) and gross inspection was performed immediately after treatment for any abnormality in the treated skin. Hair counts were performed on both crura at 1 and 3 months after the treatment, and compared with the baseline counts. Biopsies were performed in the dynamic mode treated skin at baseline and at 1 month after the treatment, and assessed with light microscopy, immunohistochemistry and transmission electron microscopy (TEM). Results All subjects completed the study. Compared with baseline, hair counts were significantly lower at 1 and 3 months post-treatment with no significant difference between the static and dynamic laser depilation modes, nor in the severity of the pain experienced during the procedure. Histologically, degenerative changes in the hair follicles were noted immediately after laser treatment. At one month, cystic formation was seen in the hair follicles showing a strong tendency towards apoptotic cell death. Conclusions With the diode laser system and at the parameters used in the present study, high depilation efficacy was seen with no significant difference between the static and dynamic modes. Interestingly, good long-term depilation is probably a result of induced apoptotic cell death in the follicles rather than any other mechanism. PMID:28740327

Age-associated decrease in GDNF and its cognate receptor GFRα-1 protein expression in human skin.

PubMed

Adly, Mohamed A; Assaf, Hanan A; Hussein, Mahmoud Rezk Abdelwahed

2016-06-01

Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that 'GDNF and GFRα-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5-18 years), adults (19-60 years) and the elderly (61-81 years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin-biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFRα-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFRα-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFRα-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFRα-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFRα-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFRα-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

A Comparison of Vertical and Transverse Sections in the Histological Diagnosis of Alopecia Areata Scalp Biopsy Specimens

PubMed Central

Singh, Kanika; Sharma, Sonal; Singh, Usha Rani; Bhattacharya, Sambit Nath

2016-01-01

Context: Both vertical and transverse sections are used for the diagnosis of alopecia areata. However when a single biopsy is submitted the pathologist has to decide which type is better. Aims: To compare the diagnostic histological features in vertical and transverse sections in alopecia areata scalp biopsy specimens. Settings and Design: Tertiary Care Hospital. Comparative Study. Materials and Methods: A total of 30 patients were enrolled in the study. Two four mm punch biopsy were taken. One was used to take vertical sections and the other for transverse section and histological features of alopecia areata noted in both. Statistical Analysis Used: Chi-square test, percentage. Results: Diagnosis of alopecia areata could be made in 30 (100%) cases in transverse sections and 28 cases (93.3%) in vertical sections. The number of hair follicles available for evaluation was more in the transverse section. Nanogen follicles and miniaturization of follicles were better visualized in the transverse sections. However the catagen and telogen follicles were noted in both vertical and transverse sections but the number and the ratio of anagen and telogen hair follicles could be better assessed in the transverse sections. Presence of peribulbar lymphocytic infiltrate, eosinophils and pigment casts were noted in both transverse and vertical sections. Conclusions: Transverse sections provide a better assessment of the histological features of alopecia areata than vertical sections and thus should be preferred. PMID:27625562

A Comparison of Vertical and Transverse Sections in the Histological Diagnosis of Alopecia Areata Scalp Biopsy Specimens.

PubMed

Singh, Kanika; Sharma, Sonal; Singh, Usha Rani; Bhattacharya, Sambit Nath

2016-01-01

Both vertical and transverse sections are used for the diagnosis of alopecia areata. However when a single biopsy is submitted the pathologist has to decide which type is better. To compare the diagnostic histological features in vertical and transverse sections in alopecia areata scalp biopsy specimens. Tertiary Care Hospital. Comparative Study. A total of 30 patients were enrolled in the study. Two four mm punch biopsy were taken. One was used to take vertical sections and the other for transverse section and histological features of alopecia areata noted in both. Chi-square test, percentage. Diagnosis of alopecia areata could be made in 30 (100%) cases in transverse sections and 28 cases (93.3%) in vertical sections. The number of hair follicles available for evaluation was more in the transverse section. Nanogen follicles and miniaturization of follicles were better visualized in the transverse sections. However the catagen and telogen follicles were noted in both vertical and transverse sections but the number and the ratio of anagen and telogen hair follicles could be better assessed in the transverse sections. Presence of peribulbar lymphocytic infiltrate, eosinophils and pigment casts were noted in both transverse and vertical sections. Transverse sections provide a better assessment of the histological features of alopecia areata than vertical sections and thus should be preferred.

Efficacy of topical tofacitinib in promoting hair growth in non-scarring alopecia: possible mechanism via VEGF induction.

PubMed

Meephansan, Jitlada; Thummakriengkrai, J; Ponnikorn, S; Yingmema, W; Deenonpoe, R; Suchonwanit, P

2017-11-01

Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation. mRNA and protein expression of anagen-maintaining growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), were determined via RT-PCR and ELISA, respectively. Tofacitinib-treated mice exhibited more hair regrowth than either minoxidil-treated or control mice did between day 7 and 21 (P < 0.05). Topical tofacitinib also promoted more rapid hair growth rate than topical minoxidil or control did (P < 0.001). Histopathology showed a distinct increase in the number of hair follicles, mostly in the anagen phase, in the tofacitinib-treated group. Hair follicles in the minoxidil- and vehicle-treated groups were more often classified as catagen and anagen. VEGF mRNA and protein expression in the tofacitinib-treated group was significantly greater than those in the other groups (P < 0.05). IGF-1 mRNA expression was not upregulated in tofacitinib-treated mice. Topical tofacitinib is effective in promoting hair growth, and the possible mechanism involves increased VEGF levels and lowered inflammation. This study will help develop a new therapeutic option for non-scarring alopecia.

Hair growth activity of Crataegus pinnatifida on C57BL/6 mouse model.

PubMed

Shin, Heon-Sub; Lee, Jung-Min; Park, Sang-Yong; Yang, Jung-Eun; Kim, Ju-Han; Yi, Tae-Hoo

2013-09-01

Crataegus pinnatifida has a long history of use in traditional oriental herbal medicine to stimulating digestion and improving blood circulation. Based on nutrition of hair, the present study was conducted to assess the effect of C. pinnatifida extract on hair growth using mouse model and its mechanisms of action. The C. pinnatifida extract containing the contents of total polyphenol of 5.88□0.82 g gallic acid/100 g extract and proanthocyanidin of 9.15□1.58 mg cyaniding chloride/100 g extract was orally administered daily at a dosage of 50 mg/kg weight to the 7-week-old C57BL/6 mice in telogen. The C. pinnatifida extract promoted hair growth by inducing anagen phase in mice in telogen, reflected by color of skin, thickness of hair shaft, and density of hair. The ratio of anagento telogen was determined by shape of hair follicles in vertically sectioned slide and increased by oral administration of C. pinnatifida extract. The number and the size of hair follicles were also enlarged, indicating anagen phase induction. The proliferation of human dermal papilla cells (hDPC) was accelerated by addition of C. pinnatifida extract, which activated the signaling of mitogen-activated protein kinases (Erk, p-38, and JNK) and Akt. Moreover, the ratio of Bcl-2/Bax as the determinant of cell fate was also raised in skin. These results suggest that the C. pinnatifida extract promotes hair growth by inducing anagen phase, which might be mediated by the activation of cellular signalings that enhance the survival of cultured hDPC and the increase of the ratio of Bcl-2 to Bax that protects cells against cell death. Copyright © 2012 John Wiley & Sons, Ltd.

Folliculitis

MedlinePlus

... this page: //medlineplus.gov/ency/article/000823.htm Folliculitis To use the sharing features on this page, please enable JavaScript. Folliculitis is inflammation of one or more hair follicles. ...

Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re-epithelialization.

PubMed

Garcin, Clare L; Ansell, David M; Headon, Denis J; Paus, Ralf; Hardman, Matthew J

2016-05-01

The cutaneous healing response has evolved to occur rapidly, in order to minimize infection and to re-establish epithelial homeostasis. Rapid healing is achieved through complex coordination of multiple cell types, which importantly includes specific cell populations within the hair follicle (HF). Under physiological conditions, the epithelial compartments of HF and interfollicular epidermis remain discrete, with K15(+ve) bulge stem cells contributing progeny for HF reconstruction during the hair cycle and as a basis for hair shaft production during anagen. Only upon wounding do HF cells migrate from the follicle to contribute to the neo-epidermis. However, the identity of the first-responding cells, and in particular whether this process involves a direct contribution of K15(+ve) bulge cells to the early stage of epidermal wound repair remains unclear. Here we demonstrate that epidermal injury in murine skin does not induce bulge activation during early epidermal wound repair. Specifically, bulge cells of uninjured HFs neither proliferate nor appear to migrate out of the bulge niche upon epidermal wounding. In support of these observations, Diphtheria toxin-mediated partial ablation of K15(+ve) bulge cells fails to delay wound healing. Our data suggest that bulge cells only respond to epidermal wounding during later stages of repair. We discuss that this response may have evolved as a protective safeguarding mechanism against bulge stem cell exhaust and tumorigenesis. Stem Cells 2016;34:1377-1385. © 2016 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Treatment of folliculitis decalvans using intensity-modulated radiation via tomotherapy.

PubMed

Elsayad, Khaled; Kriz, Jan; Haverkamp, Uwe; Plachouri, Kerasia-Maria; Jeskowiak, Antonia; Sunderkötter, Cord; Eich, Hans Theodor

2015-11-01

Folliculitis decalvans (FD) is a form of primary neutrophilic scarring alopecia that is characterized clinically by chronic suppurative folliculitis and often associated with pruritus or even pain. Treatment of FD is often difficult. Herein, we report a case of recalcitrant and painful folliculitis decalvans refractory to antibiotic and anti-inflammatory therapies, which was successfully treated by intensity-modulated radiotherapy (IMRT) in order to irreversibly eliminate hair follicles that prove to be one etiological trigger. A 45-year-old male patient with a refractory FD presented with a crusting suppurative folliculitis and atrophic scarring patches on the scalp associated with pain and pruritus. We attempted relief of symptoms by reducing scalp inflammation and eliminating hair follicles through radiation. We delivered 11.0 Gy in two radiation series using tomotherapy, 5.0 Gy in 5 equivalent fractions as a first radiation course. The symptoms markedly decreased but did not totally disappear. Therefore, we delivered a second radiation series 4 months later with an additional 6 Gy. This led to almost complete epilation on the scalp and abolished pain and pruritus on the capillitium. The patient was regularly followed up until 26 months after radiotherapy. Draining lesions or exudation did not recur. He only experienced discrete hair regrowth in the occipital region with folliculitis 12 months after radiotherapy. These residual lesions are currently treated with laser epilation therapy. A radical approach to eliminating hair follicles by repeated radiation therapy may induce lasting relief of symptoms in chronic suppurative FD associated with persistent trichodynia.

Evidence of mating readiness in certain bats killed by wind turbines

USGS Publications Warehouse

Cryan, Paul M.; Jameson, Joel W.; Baerwald, Erin F.; Willis, Craig K.R.; Barclay, Robert M.R.; Snider, Elise A.; Crichton, Elizabeth G.

2010-01-01

like structures. In this pilot study we histologically examined reproductive tracts of hoary bats (Lasiurus cinereus) and silver-haired bats (Lasionycteris noctivagans), found dead beneath wind turbines, for evidence of mating or mating readiness. We sampled 61 L. cinereus and 31 L. noctivagans killed by turbines in New York, USA, and Alberta and Manitoba, Canada between early July and late September. By August most adult male L. cinereus had sperm in the caudae epididymides (CE), indicating readiness to mate. About half of juvenile male hoary bats had sperm in their CE by August, revealing reproductive activity just months after birth. Sperm were seen in the uterus ofthe only adult female hoary bat collected in September, but we found no sperm in the other 17 females sampled in previous months. Ovaries of most adult and juvenile female L. cinereus had growing follicles, but they did not appear to be in estrus. Evidence of sperm in L. noctivagans was more limited, yet sperm were found in the CE of some adult and juvenile males. No female L. noctivagans contained sperm, but most adults and juveniles had growing follicles. These results indicate that adult and juvenile males of each species were ready to mate when they were killed by wind turbines, although evidence of copulation with females was limited. Results were insufficient to disprove the mating hypothesis - more thorough analysis of bats killed by turbines from late August through October and from a broader geographic area will be the next important step in assessing its merit.

Epidermal Notch signalling: differentiation, cancer and adhesion.

PubMed

Watt, Fiona M; Estrach, Soline; Ambler, Carrie A

2008-04-01

The Notch pathway plays an important role in regulating epidermal differentiation. Notch ligands, receptors and effectors are expressed in a complex and dynamic pattern in embryonic and adult skin. Genetic ablation or activation of the pathway reveals that Notch signalling promotes differentiation of the hair follicle, sebaceous gland and interfollicular epidermal lineages and that Notch acts as an epidermal tumour suppressor. Notch signalling interacts with a range of other pathways to fulfil these functions and acts via RBP-Jkappa dependent and independent mechanisms. The effects on differentiation can be cell autonomous and non-autonomous, and Notch contributes to stem cell clustering via modulation of cell adhesion.

Ambulatory Visits Among Members of the Active Component, U.S. Armed Forces, 2011

DTIC Science & Technology

2012-04-01

immunity (240 - 279) 119,054 Skin and subcutaneous tissue (680 - 709) 315,578 Disorders of lipoid metabolism 35,989 30.2 Other cellulitis and abscess 56,135...hemorrhagic conditions 1,020 10.0 Other cellulitis and abscess 10,145 11.4 Diseases of white blood cells 865 8.5 Diseases of hair and hair follicles 7,635

Diguanoside tetraphosphate (Gp₄G) is an epithelial cell and hair growth regulator.

PubMed

Severino, Divinomar; Zorn, Telma M T; Micke, Gustavo A; Costa, Ana C O; Silva, José Roberto M C; Nogueira, Leandro F; Kowaltowski, Alicia J; Kowaltowski, Alica J; Baptista, Maurício S

2011-01-01

Our goal was to study the effect of Gp₄G on skin tissues and unravel its intracellular action mechanisms. The effects of Gp₄G formulation, a liposomic solution of Artemia salina extract, on several epidermal, depmal, and hair follicle structures were quantified. A 50% increase in hair length and a 30% increase in the number of papilla cells were explained by the changes in the telogen/anagen hair follicle phases. Increasing skin blood vessels and fibroblast activation modified collagen arrangement in dermal tissues. Imunohistochemical staining revealed expressive increases of versican (VER) deposition in the treated animals (68%). Hela and fibroblast cells were used as in vitro models. Gp₄G enters both cell lines, with a hyperbolic saturation profile inducing an increase in the viabilities of Hela and fibroblast cells. Intracellular ATP and other nucleotides were quantified in Hela cells showing a 38% increase in intracellular ATP concentration and increases in the intracellular concentration of tri- , di- , and monophosphate nucleosides, changing the usual quasi-equilibrium state of nucleotide concentrations. We propose that this change in nucleotide equilibrium affects several biochemical pathways and explains the cell and tissue activations observed experimentally.

Hair plucking, stress, and urinary cortisol among captive bonobos (Pan paniscus).

PubMed

Brand, Colin M; Boose, Klaree J; Squires, Erica C; Marchant, Linda F; White, Frances J; Meinelt, Audra; Snodgrass, J Josh

2016-09-01

Hair plucking has been observed in many captive primate species, including the great apes; however, the etiology of this behavioral pattern is poorly understood. While this behavior has not been reported in wild apes, an ethologically identical behavior in humans, known as trichotillomania, is linked to chronic psychosocial stress and is a predominantly female disorder. This study examines hair plucking (defined here as a rapid jerking away of the hair shaft and follicle by the hand or mouth, often accompanied by inspection and consumption of the hair shaft and follicle) in a captive group of bonobos (N = 13) at the Columbus Zoo and Aquarium in Columbus, Ohio. Plucking data were collected using behavior and all-occurrence sampling; 1,450 social and self-directed grooming bouts were recorded during 128 hr of observation. Twenty-one percent of all grooming bouts involved at least one instance of plucking. Urine samples (N = 55) were collected and analyzed for the stress hormone cortisol. Analyses of urinary cortisol levels showed a significant positive correlation between mean cortisol and self-directed plucking for females (r = 0.88, P < 0.05) but not for males (r = -0.73, P = 0.09). These results demonstrate an association between relative self-directed hair plucking and cortisol among female bonobos. This is the first study to investigate the relationship between hair plucking and cortisol among apes. Overall, these data add to our knowledge of a contemporary issue in captive ape management. Zoo Biol. 35:415-422, 2016. © Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Black women's hair: the main scalp dermatoses and aesthetic practices in women of African ethnicity *

PubMed Central

Tanus, Aline; Oliveira, Camila Caberlon Cruz; Villarreal, Delky Johanna Villarreal; Sanchez, Fernando Andres Vargas; Dias, Maria Fernanda Reis Gavazzoni

2015-01-01

Afro-ethnic hair is different from Caucasian and Asian hair and has unique features. Ethnic hair is more prone to certain conditions or diseases. Such diseases are not only related to the fragile inner structure of the hair, but also to the cultural habits of hairstyles that often exert traction forces upon the pilosebaceous follicle. Women with African hair subject their hair to chemical treatments such as hair straightening and relaxing, and thus modify the structure of their hair shaft, making it more susceptible to damage. For this reason, hair complaints are common among black women and represent a diagnostic challenge to the dermatologist, requiring a thorough clinical examination of the hair and scalp, and a detailed medical history of the patient. The purpose of this review is to warn of the potential side effects and sequelae related to hairstyles and hair treatments used by black women, and to highlight the major diseases that affect this ethnicity. PMID:26375213

Hair regrowth through wound healing process after ablative fractional laser treatment in a murine model.

PubMed

Bae, Jung Min; Jung, Han Mi; Goo, Boncheol; Park, Young Min

2015-07-01

Alopecia is one of the most common dermatological problems in the elderly; however, current therapies for it are limited by low efficacy and undesirable side effects. Although clinical reports on fractional laser treatment for various alopecia types are increasing, the exact mechanism remains to be clarified. The purposes of this study were to demonstrate the effect of ablative fractional laser treatment on hair follicle regrowth in vivo and investigate the molecular mechanism after laser treatment. Ablative CO2 fractional laser was applied to the shaved dorsal skin of 7-week-old C57BL/6 mice whose hair was in the telogen stage. After 12 mice were treated at various energy (10-40 mJ/spot) and density (100-400 spots/cm(2) ) settings to determine the proper dosage for maximal effect. Six mice were then treated at the decided dosage and skin specimens were sequentially obtained by excision biopsy from the dorsal aspect of each mouse. Tissue samples were used for the immunohistochemistry and reverse transcription polymerase chain reaction assays to examine hair follicle status and their related molecules. The most effective dosage was the 10 mJ/spot and 300 spots/cm(2) setting. The anagen conversion of hair was observed in the histopathological examination, while Wnt/β-catenin expression was associated with hair regrowth in the immunohistochemistry and molecular studies. Ablative fractional lasers appear to be effective for inducing hair regrowth via activation of the Wnt/β-catenin pathway in vivo. Our findings indicate that fractional laser treatment can potentially be developed as new treatment options for stimulating hair regrowth. © 2015 Wiley Periodicals, Inc.

Minoxidil use in dermatology, side effects and recent patents.

PubMed

Rossi, Alfredo; Cantisani, Carmen; Melis, Luca; Iorio, Alessandra; Scali, Elisabetta; Calvieri, Stefano

2012-05-01

Minoxidil, a vasodilator medication known for its ability to slow or stop hair loss and promote hair regrowth, was first introduced, exclusively as an oral drug, to treat high blood pressure. It was however discovered to have the important side-effect of increasing growth or darkening of fine body hairs; this led to the development of a topical formulation as a 2% concentration solution for the treatment of female androgenic alopecia or 5% for treating male androgenic alopecia. Measurable changes disappear within months after discontinuation of treatment. The mechanism by which it promotes hair growth is not fully understood. Minoxidil is a potassium channel opener, causing hyperpolarization of cell membranes and it is also a vasodilator, it is speculated that, by widening blood vessels and opening potassium channels, it allows more oxygen, blood and nutrients to the follicle. This can also cause follicles in the telogen phase to shed, usually soon to be replaced by new, thicker hairs in a new anagen phase. It needs to be applied regularly, once or twice daily, for hair gained to be maintained, and side effects are common. The most common adverse reactions of the topical formulation are limited to irritant and allergic contact dermatitis on the scalp. There have been cases of allergic reactions to the nonactive ingredient propylene glycol, which is found in some topical solution especially if they are galenic. Increased hair loss which can occur during Minoxidil use, is due to the synchronization of the hair cycle that the treatment induces. In this review, we described its mechanism of action, use in dermatology and some patents related to alternative treatment of allergic reactions due to its use.

Oral zinc sulphate causes murine hair hypopigmentation and is a potent inhibitor of eumelanogenesis in vivo.

PubMed

Plonka, P M; Handjiski, B; Michalczyk, D; Popik, M; Paus, R

2006-07-01

C57BL/6 a/a mice have been widely used to study melanogenesis, including in electron paramagnetic resonance (EPR) studies. Zinc cations modulate melanogenesis, but the net effect of Zn2+ in vivo is unclear, as the reported effects of Zn2+ on melanogenesis are ambiguous: zinc inhibits tyrosinase and glutathione reductase in vitro, but also enhances the activity of dopachrome tautomerase (tyrosinase-related protein-2) and has agonistic effects on melanocortin receptor signalling. To determine in a C57BL/6 a/a murine pilot study whether excess zinc ions inhibit, enhance or in any other way alter hair follicle melanogenesis in vivo, and to test the usefulness of EPR for this study. ZnSO(4).7H2O was continuously administered orally to C57BL/6 a/a mice during spontaneous and depilation-induced hair follicle cycling (20 mg mL-1; in drinking water; mean+/-SD daily dose 1.2+/-0.53 mL), and hair pigmentation was examined macroscopically, by routine histology and by EPR. Oral zinc cations induced a bright brown lightening of new hair shafts produced during anagen, but without inducing an EPR-detectable switch from eumelanogenesis to phaeomelanogenesis. The total content of melanin in the skin and hair shafts during the subsequent telogen phase, i.e. after completion of a full hair cycle, was significantly reduced in Zn-treated mice (P=0.0005). Compared with controls, melanin granules in precortical hair matrix keratinocytes, hair bulb melanocytes and hair shafts of zinc-treated animals were reduced and poorly pigmented. Over the course of several hair cycles, lasting hair shaft depigmentation was seen during long-term exposure to high-dose oral Zn2+. High-dose oral Zn2+ is a potent downregulator of eumelanin content in murine hair shafts in vivo. The C57BL/6 mouse model offers an excellent tool for further dissecting the as yet unclear underlying molecular basis of this phenomenon, while EPR technology is well suited for the rapid, qualitative and quantitative monitoring of hair pigmentation changes.

Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin

PubMed Central

Tong, Tao; Kim, Nahyun; Park, Taesun

2015-01-01

We observed that oleuropein, the main constituent of the leaves and unprocessed olive drupes of Olea europaea, protected mice from high-fat diet-induced adiposity by up-regulation of genes involved in Wnt10b-mediated signaling in adipose tissue. The activation of Wnt/β-catenin pathway is also well established to positively regulate the anagen phase of hair growth cycle in mice skin. Methodology and Principal Findings Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day) to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression. Conclusions and Significance These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue. PMID:26060936

Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells.

PubMed

Lachgar, S; Charveron, M; Gall, Y; Bonafe, J L

1998-03-01

The hair follicle dermal papilla which controls hair growth, is characterized in the anagen phase by a highly developed vascular network. We have demonstrated in a previous study that the expression of an angiogenic growth factor called vascular endothelial growth factor (VEGF) mRNA varied during the hair cycle. VEGF mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase, but during the catagen and telogen phases. VEGF mRNA is less strongly expressed. This involvement of VEGF during the hair cycle allowed us to determine whether VEGF mRNA expression by DPC was regulated by minoxidil. In addition, the effect of minoxidil on VEGF protein synthesis in both cell extracts and DPC-conditioned medium, was investigated immunoenzymatically. Both VEGF mRNA and protein were significantly elevated in treated DPC compared with controls. DPC incubated with increasing minoxidil concentrations (0.2, 2, 6, 12 and 24 mumol/L) induced a dose-dependent expression of VEGF mRNA. Quantification of transcripts showed that DPC stimulated with 24 mumol/L minoxidil express six times more VEGF mRNA than controls. Similarly, VEGF protein production increases in cell extracts and conditioned media following minoxidil stimulation. These studies strongly support the likely involvement of minoxidil in the development of dermal papilla vascularization via a stimulation of VEGF expression, and support the hypothesis that minoxidil has a physiological role in maintaining a good vascularization of hair follicles in androgenetic alopecia.

Skin age testing criteria: characterization of human skin structures by 500 MHz MRI multiple contrast and image processing.

PubMed

Sharma, Rakesh

2010-07-21

Ex vivo magnetic resonance microimaging (MRM) image characteristics are reported in human skin samples in different age groups. Human excised skin samples were imaged using a custom coil placed inside a 500 MHz NMR imager for high-resolution microimaging. Skin MRI images were processed for characterization of different skin structures. Contiguous cross-sectional T1-weighted 3D spin echo MRI, T2-weighted 3D spin echo MRI and proton density images were compared with skin histopathology and NMR peaks. In all skin specimens, epidermis and dermis thickening and hair follicle size were measured using MRM. Optimized parameters TE and TR and multicontrast enhancement generated better MRI visibility of different skin components. Within high MR signal regions near to the custom coil, MRI images with short echo time were comparable with digitized histological sections for skin structures of the epidermis, dermis and hair follicles in 6 (67%) of the nine specimens. Skin % tissue composition, measurement of the epidermis, dermis, sebaceous gland and hair follicle size, and skin NMR peaks were signatures of skin type. The image processing determined the dimensionality of skin tissue components and skin typing. The ex vivo MRI images and histopathology of the skin may be used to measure the skin structure and skin NMR peaks with image processing may be a tool for determining skin typing and skin composition.

Skin age testing criteria: characterization of human skin structures by 500 MHz MRI multiple contrast and image processing

NASA Astrophysics Data System (ADS)

Sharma, Rakesh

2010-07-01

Ex vivo magnetic resonance microimaging (MRM) image characteristics are reported in human skin samples in different age groups. Human excised skin samples were imaged using a custom coil placed inside a 500 MHz NMR imager for high-resolution microimaging. Skin MRI images were processed for characterization of different skin structures. Contiguous cross-sectional T1-weighted 3D spin echo MRI, T2-weighted 3D spin echo MRI and proton density images were compared with skin histopathology and NMR peaks. In all skin specimens, epidermis and dermis thickening and hair follicle size were measured using MRM. Optimized parameters TE and TR and multicontrast enhancement generated better MRI visibility of different skin components. Within high MR signal regions near to the custom coil, MRI images with short echo time were comparable with digitized histological sections for skin structures of the epidermis, dermis and hair follicles in 6 (67%) of the nine specimens. Skin % tissue composition, measurement of the epidermis, dermis, sebaceous gland and hair follicle size, and skin NMR peaks were signatures of skin type. The image processing determined the dimensionality of skin tissue components and skin typing. The ex vivo MRI images and histopathology of the skin may be used to measure the skin structure and skin NMR peaks with image processing may be a tool for determining skin typing and skin composition.

Pigmented Epithelioid Melanocytoma (PEM)/Animal Type Melanoma (ATM): Quest for an Origin. Report of One Unusual Case Indicating Follicular Origin and Another Arising in an Intradermal Nevus †

PubMed Central

Tarasen, Ashley; Carlson, J. Andrew; Leonard, M. Kathryn; Merlino, Glenn; Kaetzel, David

2017-01-01

Pigmented epithelioid melanocytoma (PEM) is a tumor encompassing epithelioid blue nevus of Carney complex (EBN of CNC) and was previously termed animal-type melanoma. Histologically PEMs are heavily pigmented spindled and epithelioid dermal melanocytic tumors with infiltrative borders, however, their origin remains unclear. Stem cells for the epidermis and hair follicle are located in the bulge area of the hair follicle with the potential to differentiate into multiple lineages. Multiple cutaneous carcinomas, including follicular cutaneous squamous cell carcinoma (FSCC), are thought to arise from stem cells in the follicular bulge. We present two cases of PEM/ATM in a 63 year-old male on the scalp with follicular origin and a 72 year-old female on the upper back arising in an intradermal nevus. Biopsy of both cases revealed a proliferation of heavily pigmented dermal nests of melanocytes with atypia. The Case 1 tumor was in continuation with the outer root sheath of the hair follicle in the bulge region. Case 2 arose in an intradermal melanocytic nevus. Rare mitotic figures, including atypical mitotic figures, were identified in both cases. We present two cases of PEM, with histologic evidence suggesting two origins: one from the follicular bulb and one from an intradermal nevus. PMID:28809777

The targeted overexpression of a Claudin mutant in the epidermis of transgenic mice elicits striking epidermal and hair follicle abnormalities.

PubMed

Troy, Tammy-Claire; Turksen, Kursad

2007-06-01

Skin is one of the largest organs of the body, and is formed during development through a highly orchestrated process involving mesenchymal-epithelial interactions, cell commitment, and terminal differentiation. It protects against microorganism invasion and UV irradiation, inhibits water loss, regulates body temperature, and is an important part of the immune system. Using transgenic mouse technology, we have demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are intricately involved in cell signaling during epidermal differentiation and that an epidermal suprabasal overexpression of Cldn6 results in a perturbed epidermal terminal differentiation program with distinct phenotypic abnormalities. To delineate the role of the Cldn cytoplasmic tail domain in epidermal differentiation, we engineered transgenic mice targeting the overexpression of a Cldn6 cytoplasmic tail-truncation mutant in the epidermis. Transgenic mice were characterized by a lethal barrier dysfunction in addition to the existence of hyperproliferative squamous invaginations/cysts replacing hair follicles. Immunohistochemical analysis revealed an epidermal cytoplasmic accumulation of Cldn6, Cldn11, Cldn12, and Cldn18, downregulation of Cldn1 and aberrant expression of various classical markers of epidermal differentiation; namely the basal keratins as well as K1, involucrin, loricrin, and filaggrin. Collectively these studies suggest an important role for Cldns in epidermal/hair follicle differentiation programs likely involving cross talk to signaling pathways (e.g., Notch) directing cell fate selection and differentiation.

Development of a Two-Dimensional Model for Predicting Transdermal Permeation with the Follicular Pathway: Demonstration with a Caffeine Study.

PubMed

Kattou, Panayiotis; Lian, Guoping; Glavin, Stephen; Sorrell, Ian; Chen, Tao

2017-10-01

The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in lipid, corneocytes, viable dermis, dermis and systemic circulation are calculated as reported previously [Pharm Res 33 (2016) 1602]. The mass transfer and partition properties in sebum are collected from existing literature. None of the model input parameters was fit to the clinical data with which the model prediction is compared. The integrated model has been applied to predict the published clinical data of transdermal permeation of caffeine. The relative importance of the follicular pathway is analysed. Good agreement of the model prediction with the clinical data has been obtained. The simulation confirms that for caffeine the follicular route is important; the maximum bioavailable concentration of caffeine in systemic circulation with open hair follicles is predicted to be 20% higher than that when hair follicles are blocked. The follicular pathway contributes to not only short time fast penetration, but also the overall systemic bioavailability. With such in silico model, useful information can be obtained for caffeine disposition and localised delivery in lipid, corneocytes, viable dermis, dermis and the hair follicle. Such detailed information is difficult to obtain experimentally.

Hair Follicle-Associated Pluripotent (HAP) Stem Cells in Gelfoam® Histoculture for Use in Spinal Cord Repair.

PubMed

Liu, Fang; Hoffman, Robert M

2018-01-01

The stem cell marker, nestin, is expressed in the hair follicle, both in cells in the bulge area (BA) and the dermal papilla (DP). Nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells of both the BA and DP have been previously shown to be able to form neurons, heart muscle cells, and other non-follicle cell types. The ability of the nestin-expressing HAP stem cells from the BA and DP to repair spinal cord injury was compared. Nestin-expressing HAP stem cells from both the BA and DP grew very well on Gelfoam ® . The HAP stem cells attached to the Gelfoam ® within 1 h. They grew along the grids of the Gelfoam ® during the first 2 or 3 days. Later they spread into the Gelfoam ® . After transplantation of Gelfoam ® cultures of nestin-expressing BA or DP HAP stem cells into the injured spinal cord (including the Gelfoam ® ) nestin-expressing BA and DP cells were observed to be viable over 100 days post-surgery. Hematoxylin and eosin (H&E) staining showed connections between the transplanted cells and the host spine tissue. Immunohistochemistry showed many Tuj1-, Isl 1/2, and EN1-positive cells and nerve fibers in the transplanted area of the spinal cord after BA Gelfoam ® or DP Gelfoam ® cultures were transplanted to the spine. The spinal cord of mice was injured to effect hind-limb paralysis. Twenty-eight days after transplantation with BA or DP HAP stem cells on Gelfoam ® to the injured area of the spine, the mice recovered normal locomotion.

Acne

MedlinePlus

Acne is a common skin disease that causes pimples. Pimples form when hair follicles under your skin ... neck, back, chest, and shoulders. Anyone can get acne, but it is common in teenagers and young ...

Comparative Transcriptome Analysis of Fetal Skin Reveals Key Genes Related to Hair Follicle Morphogenesis in Cashmere Goats.

PubMed

Gao, Ye; Wang, Xiaolong; Yan, Hailong; Zeng, Jie; Ma, Sen; Niu, Yiyuan; Zhou, Guangxian; Jiang, Yu; Chen, Yulin

2016-01-01

Cashmere goat skin contains two types of hair follicles (HF): primary hair follicles (PHF) and secondary hair follicles (SHF). Although multiple genetic determinants associated with HF formation have been identified, the molecules that determine the independent morphogenesis of HF in cashmere goats remain elusive. The growth and development of SHF directly influence the quantity and quality of cashmere production. Here, we report the transcriptome profiling analysis of nine skin samples from cashmere goats using 60- and 120-day-old embryos (E60 and E120, respectively), as well as newborns (NB), through RNA-sequencing (RNA-seq). HF morphological changes indicated that PHF were initiated at E60, with maturation from E120, while differentiation of SHF was identified at E120 until formation of cashmere occurred after birth (NB). The RNA-sequencing analysis generated over 20.6 million clean reads from each mRNA library. The number of differentially expressed genes (DEGs) in E60 vs. E120, E120 vs. NB, and E60 vs. NB were 1,024, 0 and 1,801, respectively, indicating that no significant differences were found at transcriptomic levels between E120 and NB. Key genes including B4GALT4, TNC, a-integrin, and FGFR1, were up-regulated and expressed in HF initiation from E60 to E120, while regulatory genes such as GPRC5D, PAD3, HOXC13, PRR9, VSIG8, LRRC15, LHX2, MSX-2, and FOXN1 were up-regulated and expressed in HF keratinisation and hair shaft differentiation from E120 and NB to E60. Several genes belonging to the KRT and KRTAP gene families were detected throughout the three HF developmental stages. The transcriptional trajectory analyses of all DEGs indicated that immune privilege, glycosaminoglycan biosynthesis, extracellular matrix receptor interaction, and growth factor receptors all played dominant roles in the epithelial-mesenchymal interface and HF formation. We found that the Wnt, transforming growth factor-beta/bone morphogenetic protein, and Notch family members played vital roles in HF differentiation and maturation. The DEGs we found could be attributed to the generation and development of HF, and thus will be critically important for improving the quantity and quality of fleece production in animals for fibres.