Roles for PDGF-A and sonic hedgehog in development of mesenchymal components of the hair follicle

Skin appendages, such as hair, develop as a result of complex reciprocal signaling between epithelial and mesenchymal cells. These interactions are not well understood at the molecular level. Platelet-derived growth factor-A (PDGF-A) is expressed in the developing epidermis and hair follicle epithelium, and its receptor PDGF-Ralpha is expressed in associated mesenchymal structures. Here we have characterized the skin and hair phenotypes of mice carrying a null mutation in the PDGF-A gene. Postnatal PDGF-A−/− mice developed thinner dermis, misshapen hair follicles, smaller dermal papillae, abnormal dermal sheaths and thinner hair, compared with wild-type siblings. BrdU labeling showed reduced cell proliferation in the dermis and in the dermal sheaths of PDGF-A−/− skin. PDGF-A−/− skin transplantation to nude mice led to abnormal hair formation, reproducing some of the features of the skin phenotype of PDGF-A−/− mice. Taken together, expression patterns and mutant phenotypes suggest that epidermal PDGF-A has a role in stimulating the proliferation of dermal mesenchymal cells that may contribute to the formation of dermal papillae, mesenchymal sheaths and dermal fibroblasts. Finally, we show that sonic hedgehog (shh)−/− mouse embryos have disrupted formation of dermal papillae. Such embryos fail to form pre-papilla aggregates of postmitotic PDGF-Ralpha-positive cells, suggesting that shh has a critical role in the assembly of the dermal papilla.

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Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp

Journal of Endocrinology ◽

10.1677/joe.0.1560059 ◽

1998 ◽

Vol 156 (1) ◽

pp. 59-65 ◽

Cited By ~ 147

Author(s):

NA Hibberts ◽

AE Howell ◽

VA Randall

Keyword(s):

Androgen Receptor ◽

Hair Follicle ◽

Androgen Receptors ◽

Scalp Hair ◽

Dermal Papilla ◽

Hair Follicles ◽

Dermal Fibroblasts ◽

Good Precision ◽

Dermal Papilla Cells

Androgens can gradually transform large scalp hair follicles to smaller vellus ones, causing balding. The mechanisms involved are unclear, although androgens are believed to act on the epithelial hair follicle via the mesenchyme-derived dermal papilla. This study investigates whether the levels and type of androgen receptors in primary lines of cultured dermal papilla cells derived from balding scalp hair follicles differ from those of follicles from non-balding scalp. Androgen receptor content was measured by saturation analysis using the non-metabolisable androgen, [3H]mibolerone (0.05-10 nM) in a 9-10 point assay. Pubic dermal fibroblasts and Shionogi cells were examined as positive controls. Repetitive assays of Shionogi cells showed good precision in the levels of androgen receptor content (coefficient of variation = 3.7%). Specific, high affinity, low capacity androgen receptors were detected in dermal papilla cells from both balding and non-balding follicles. Balding cells contained significantly (P < 0.01) greater levels of androgen receptors (Bmax = 0.06 +/- 0.01 fmol/10(4) cells (mean +/- S.E.M.)) than those from non-balding scalp (0.04 +/- 0.001). Competition studies with a range of steroids showed no differences in receptor binding specificity in the two cell types. The higher levels of androgen receptors in cells from balding scalp hair follicles with similar properties to those from non-balding scalp concur with the expectations from their in vivo responses to androgens. This supports the hypothesis that androgens act via the dermal papilla and suggests that cultured dermal papilla cells may offer a model system for studying androgen action in androgenetic alopecia.

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The induction of hair follicle formation in the adult hooded rat by vibrissa dermal papillae

Development ◽

10.1242/dev.23.1.219 ◽

1970 ◽

Vol 23 (1) ◽

pp. 219-236

Author(s):

R. F. Oliver

Keyword(s):

Hair Follicle ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Shaft ◽

Hair Follicles ◽

Hair Cycle ◽

Hair Bulb ◽

Essential Component ◽

Dermal Papillae

Hair follicles are essentially composed of two tissues. The inner epidermal component, which gives rise to, among other products, the keratinized hair shaft, is confluent with the surface epidermis and is ensheathed by the dermal component which is confluent with the pars papillaris of the dermis. A specialization of the dermal component is the dermal papilla which, in follicles producing hair, is enclosed by the epidermal matrix of the hair bulb and is connected to the dermal sheath by the papilla stalk. Many authorities have considered that the dermal papilla is an essential component of the hair follicle (reviews: Cohen, 1965; Oliver, 1969). It has been suggested that the dermal papilla may be involved in both the induction of follicle lengthening and hair growth during the proanagen phase (Chase, 1965) of the hair cycle, a concept now justified by direct experimentation in the vibrissa follicle at least (Oliver, 1967b), and perhaps also in determining the nature of the hair produced by a follicle.

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Smooth muscle alpha-actin is a marker for hair follicle dermis in vivo and in vitro

Journal of Cell Science ◽

10.1242/jcs.99.3.627 ◽

1991 ◽

Vol 99 (3) ◽

pp. 627-636 ◽

Cited By ~ 2

Author(s):

C.A. Jahoda ◽

A.J. Reynolds ◽

C. Chaponnier ◽

J.C. Forester ◽

G. Gabbiani

Keyword(s):

Smooth Muscle ◽

Hair Follicle ◽

Dermal Papilla ◽

Hair Follicles ◽

Dermal Papilla Cells ◽

Smooth Muscle Alpha Actin ◽

Actin Expression ◽

Alpha Actin ◽

Sheath Cells

We have examined the expression of smooth muscle alpha-actin in hair follicles in situ, and in hair follicle dermal cells in culture by means of immunohistochemistry. Smooth muscle alpha-actin was present in the dermal sheath component of rat vibrissa, rat pelage and human follicles. Dermal papilla cells within all types of follicles did not express the antigen. However, in culture a large percentage of both hair dermal papilla and dermal sheath cells were stained by this antibody. The same cells were negative when tested with an antibody to desmin. Overall, explant-derived skin fibroblasts had relatively low numbers of positively marked cells, but those from skin regions of high hair-follicle density displayed more smooth muscle alpha-actin expression than fibroblasts from areas with fewer follicles. 2-D SDS-PAGE confirmed that, unlike fibroblasts, cultured papilla cells contained significant quantities of the alpha-actin isoform. The rapid switching on of smooth muscle alpha-actin expression by dermal papilla cells in early culture, contrasts with the behaviour of smooth muscle cells in vitro, and has implications for control of expression of the antigen in normal adult systems. The very high percentage of positively marked cultured papilla and sheath cells also provides a novel marker of cells from follicle dermis, and reinforces the idea that they represent a specialized cell population, contributing to the heterogeneity of fibroblast cell types in the skin dermis, and possibly acting as a source of myofibroblasts during wound healing.

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Assessment of Prolonged Dengue Virus Infection in Dermal Fibroblasts and Hair-Follicle Dermal Papilla Cells

Viruses ◽

10.3390/v12030267 ◽

2020 ◽

Vol 12 (3) ◽

pp. 267

Author(s):

Kai-Che Wei ◽

Wan-Ju Wei ◽

Yi-Shan Liu ◽

Li-Chen Yen ◽

Tsung-Hsien Chang

Keyword(s):

Dengue Virus ◽

Hair Follicle ◽

Hair Loss ◽

Human Hair ◽

Dermal Papilla ◽

Denv Infection ◽

Dermal Fibroblasts ◽

Type I ◽

Dermal Papilla Cells

Dengue virus (DENV)-mediated hair loss is one of the post-dengue fatigue syndromes and its pathophysiology remains unknown. Whether long-term or persistent infection with DENV in the scalp results in hair loss is unclear. In this study, we cultured human dermal fibroblasts (WS1 cells) and primary human hair-follicle dermal papilla cells (HFDPCs) in the long term with DENV-2 infection. The production of virion, the expression of inflammatory and anti-virus genes, and their signaling transduction activity in the infected cells were analyzed. DENV-2 NS3 protein and DENV-2 5′ UTR RNA were detected in fibroblasts and HFDPCs that were subjected to long-term infection with DENV-2 for 33 days. A significant amount of DENV-2 virion was produced by both WS1 cells and HFDPCs in the first two days of acute infection. The virion was also detected in WS1 cells that were infected in the long term, but HFDPCs failed to produce DENV-2 after long-term culture. Type I and type III interferons, and inflammatory cytokines were highly expressed in the acute phase of DENV infection in HFPDC and WS1 cells. However, in the long-term cultured cells, modest levels of anti-viral protein genes were expressed and we observed reduced signaling activity, which was correlated with the level of virus production changes. Long-term infection of DENV-2 downregulated the expression of hair growth regulatory factors, such as Rip1, Wnt1, and Wnt4. This in vitro study shows that the long-term infection with DENV-2 in dermal fibroblasts and dermal papilla cells may be involved with the prolonged-DENV-infection-mediated hair loss of post-dengue fatigue syndrome. However, direct evidence for viral replication in the human hair of a dengue victim or animal infection model is required.

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Induction of dermal fibroblasts into dermal papilla cell-like cells in hydrogel microcapsules for enhanced hair follicle regeneration

Applied Materials Today ◽

10.1016/j.apmt.2020.100805 ◽

2020 ◽

Vol 21 ◽

pp. 100805

Author(s):

Bei Xie ◽

Mengting Chen ◽

Pinghui Ding ◽

Lei Lei ◽

Xing Zhang ◽

...

Keyword(s):

Hair Follicle ◽

Dermal Papilla ◽

Dermal Fibroblasts ◽

Dermal Papilla Cell

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Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth

International Journal of Molecular Sciences ◽

10.3390/ijms21165672 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5672

Author(s):

Kyung-Eun Ku ◽

Nahyun Choi ◽

Jong-Hyuk Sung

Keyword(s):

Hair Growth ◽

Expression Patterns ◽

Dermal Papilla ◽

Hair Follicles ◽

Hair Cycle ◽

Outer Root Sheath ◽

Dermal Papilla Cells ◽

Root Sheath ◽

Culture Models

Rab27a/b are known to play an important role in the transport of melanosomes, with their knockout causing silvery gray hair. However, the relationship between Rab27a/b and hair growth is not well known. To evaluate the role of Rab27a/b in hair cycle, we investigated the expression of Rab27a/b during hair cycling and human outer root sheath (hORS) cells. The expression of Rab27a in ORS cells was mainly detected at the anagen, whereas expression of Rab27b in ORS, and epidermal cells was strongly expressed at the telogen. Additionally, Rab27a/b were expressed in the Golgi of hORS cells. To evaluate the role of Rab27a/b in hair growth, telogen-to-anagen transition animal and vibrissae hair follicles (HFs) organ culture models were assayed using Rab27a/b siRNAs. The knockdown of Rab27a or Rab27b suppressed or promoted hair growth, respectively. These results were also confirmed in human dermal papilla cells (hDPCs) and hORS cells, showing the opposite mitogenic effects. Moreover, Rab27b knockdown increased the expression levels of various growth factors in the hDPCs and hORS cells. Overall, the opposite temporal expression patterns during hair cycling and roles for hair growth of Rab27a/b suggested that Rab27a/b might regulate the hair cycle. Therefore, our study may provide a novel solution for the development of hair loss treatment by regulating Rab27a/b levels.

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Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

Science Advances ◽

10.1126/sciadv.aba1685 ◽

2020 ◽

Vol 6 (30) ◽

pp. eaba1685 ◽

Cited By ~ 3

Author(s):

Shiqi Hu ◽

Zhenhua Li ◽

Halle Lutz ◽

Ke Huang ◽

Teng Su ◽

...

Keyword(s):

Hair Follicle ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Follicles ◽

Hair Cycle ◽

Paracrine Signaling ◽

Hair Regrowth ◽

Study Results ◽

Anagen Phase ◽

Hair Follicle Cycle

The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.

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Intercellular Adhesion Molecule-1 and Hair Follicle Regression

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540004800413 ◽

2000 ◽

Vol 48 (4) ◽

pp. 557-568 ◽

Cited By ~ 18

Author(s):

Sven Müller-Röver ◽

Silvia Bulfone-Paus ◽

Bori Handjiski ◽

Pia Welker ◽

John P. Sundberg ◽

...

Keyword(s):

Hair Follicle ◽

Adhesion Molecule ◽

Expression Patterns ◽

Intercellular Adhesion ◽

Hair Follicles ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Outer Root Sheath ◽

Cycle Dependent ◽

Connective Tissue Sheath

Although the intercellular adhesion molecule-1 (ICAM-1) is recognized for its pivotal role in inflammation and immune responses, its role in developmental systems, such as the cyclic growth (anagen) and regression (catagen) of the hair follicle, remains to be explored. Here we demonstrate that ICAM-1 expression in murine skin is even more widespread and more developmentally regulated than was previously believed. In addition to endothelial cells, selected epidermal and follicular keratinocyte subpopulations, as well as interfollicular fibroblasts, express ICAM-1. Murine hair follicles express ICAM-1 only late during morphogenesis. Thereafter, morphologically identical follicles markedly differ in their ICAM-1 expression patterns, which become strikingly hair cycle-dependent in both intra- and extrafollicular skin compartments. Minimal ICAM-1 and leukocyte function-associated (LFA-1) protein and mRNA expression is observed during early anagen and maximal expression during late anagen and catagen. Keratinocytes of the distal outer root sheath, fibroblasts of the perifollicular connective tissue sheath, and perifollicular blood vessels exhibit maximal ICAM-1 immunoreactivity during catagen, which corresponds to changes of LFA-1 expression on perifollicular macrophages. Finally, ICAM-1-deficient mice display significant catagen acceleration compared to wild-type controls. Therefore, ICAM-1 upregulation is not limited to pathological situations but is also important for skin and hair follicle remodeling. Collectively, this suggests a new and apparently nonimmunological function for ICAM-1-related signaling in cutaneous biology.

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Differential Expression of a Cutaneous Corticotropin-Releasing Hormone System

Endocrinology ◽

10.1210/en.2003-0851 ◽

2004 ◽

Vol 145 (2) ◽

pp. 941-950 ◽

Cited By ~ 126

Author(s):

Andrzej Slominski ◽

Alexander Pisarchik ◽

Desmond J. Tobin ◽

Joseph E. Mazurkiewicz ◽

Jacobo Wortsman

Keyword(s):

Human Skin ◽

Expression Patterns ◽

Mouse Skin ◽

Hair Follicles ◽

Dermal Fibroblasts ◽

Preferential Expression ◽

Eccrine Glands ◽

Species Specific ◽

Skin Function ◽

Human And Mouse

Abstract We completed the mapping of a cutaneous CRH signaling system in two species with widely different determinants of skin functions, humans and mice. In human skin, the CRH receptor (CRH-R) 1 was expressed in all major cellular populations of epidermis, dermis, and subcutis with CRH-R1α being the most prevalent isoform. The CRH-R2 gene was expressed solely in hair follicle keratinocytes and papilla fibroblasts, whereas CRH-R2 antigen was localized predominantly in hair follicles, sebaceous and eccrine glands, muscle and blood vessels. In mouse skin, the CRH-R2 gene and protein were widely expressed in all cutaneous compartments and in cultured normal and malignant melanocytes. CRH-binding protein mRNA was present in dermal fibroblasts, melanoma cells, and sc fat of human skin and undetectable in mouse skin. The urocortin II gene was expressed equally in mouse and human skin. Taken together with our previous investigations, the present studies document the preferential expression of CRH-R1 in human skin, which mirrors CRH-R2 expression patterns in human and mouse skin. They are likely reflecting different functional activities of human and mouse skin. The adnexal location of CRH-R2 suggests a role for the receptor in hair growth. The differential interspecies CRH signaling expression pattern probably reflects adaptation to species-specific skin function determinants.

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