Original Paper Cells Tissues Organs 2013;198:318–326 DOI: 10.1159/000356304

Accepted after revision: October 7, 2013 Published online: December 20, 2013

Activin B Promotes Initiation and Development of Hair Follicles in Mice Qin Jia a Min Zhang a Yanan Kong a Shixuan Chen a Yinghua Chen a Xueer Wang a Lei Zhang a Weiya Lang a Lu Zhang b Lin Zhang a a

Department of Histology and Embryology, and b Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, PR China

Key Words Activin B · Hair follicle development · Hair follicle cycle

Abstract 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. © 2013 S. Karger AG, Basel

Q.J. and M.Z. contributed equally to this work.

© 2013 S. Karger AG, Basel 1422–6405/13/1984–0318$38.00/0 E-Mail [email protected] www.karger.com/cto

Introduction

The development of hair follicles represents an excellent model for the study of key life processes such as interactions between the epidermis and cells that originate from the mesoderm, the regeneration of tissue and organs, pigment formation, wound healing, and the pathogenesis of skin cancer [Bernard, 2002]. Under normal physiological conditions, hair follicles develop according to a cycle that includes the telogen, anagen and catagen stages. The changes that occur with each stage are regulated by external factors stimulated by various signaling pathways [Krause and Foitzik, 2006]. For example, members of the transforming growth factor-β (TGF-β) superfamily play an important role in ectodermal organogen-

Abbreviations used in this paper AP BMP DP EGF H&E IRSs SG TGF-β TUNEL

alkaline phosphate bone morphogenetic protein dermal papilla epidermal growth factor hematoxylin and eosin inner root sheaths sebaceous gland transforming growth factor-β TdT-mediated dUTP-biotin nick end labeling

Dr. Lin Zhang and Dr. Lu Zhang School of Basic Medical Sciences Southern Medical University Guangzhou 510515 (PR China) E-Mail zlilyzh @ 126.com or zlulu70 @ 126.com

esis and development. In particular, activin, the activin receptor and binding antagonists, including follistatin, affect the proliferation, differentiation and apoptosis of cells during the initiation of hair follicles, during the hair cycle and during skin homeostasis and wound healing [Danilenko et al., 1996; Bamberger et al., 2005]. There are three different forms of activin that have been identified, and these include homodimers of activin A (βAβA), homodimers of activin B (βBβB) and heterodimers of activin AB (βAβB) [Werner and Alzheimer, 2006]. In transgenic mice lacking various components of the activin signaling pathways, various ectodermal pathologies have been observed, including altered pelage hair follicle initiation [McDowall et al., 2008]. At the mRNA level, activin-βA has been detected in dermal papilla (DP) cells of the hair follicle mesenchyme. In contrast, activin receptors IA, IB, II, and IIB, as well as the activin-binding antagonist follistatin, are primarily expressed in the hair follicle epithelium as part of the basal substrate, in the outer root sheath, during the proliferation of hair bulb cells, and in the interfollicular epidermis [Paus and Cotsarelis, 1999; Nakamura et al., 2003]. In combination, these observations suggest that activin A, activin receptors and follistatin play important roles in the initiation and development of hair follicles. However, whether activin B plays a role in the initiation and development of hair follicles remains unclear. In preliminary studies, activin B was found to promote the regeneration of hair follicles during wound healing [Zhang et al., 2011]. Therefore, in the present study, the effect of activin B on hair follicles in C57BL/6 mice was examined in both in vitro and in vivo assays.

skin sections (8 μm) was then assayed using the Genmed alkaline phosphates staining kit (GMS80033.2, Genmed Scientifics Inc., USA). All sections were visualized and imaged under a microscope (BX51, Olympus, Japan). Oil Red O Staining Frozen skin sections (7 μm) were fixed in 4% paraformaldehyde (Sigma) for 10 min and then cleared with 60% isopropyl alcohol. Sections were incubated with Oil Red O staining solution (Sigma) at room temperature for 15 min. After clearing sections with 60% isopropyl alcohol and distilled water, sections were additionally stained with hematoxylin and visualized under a microscope (BX51, Olympus). Hematoxylin and Eosin Staining and TdT-Mediated dUTP-Biotin Nick End-Labeling Cell Apoptosis Detection Mice were anesthetized with an intraperitoneal injection of 10% chloral hydrate (w/v; 0.003 ml/g body mass) before dorsal skins were carefully dissected and fixed in 4% paraformaldehyde. The skins were then dehydrated with a graded ethanol series, cleared in dimethylbenzene and embedded in paraffin. Sections (5 μm) were deparaffinized with immersion in dimethylbenzene and rehydrated. Hematoxylin and eosin (H&E) staining was performed according to standard procedures. Sections were then subjected to TdTmediated dUTP-biotin nick end-labeling (TUNEL) cell apoptosis detection analysis according to the procedures provided by Apoptosis Detection Kit II (MK1022, Boster, Wuhan, China). Staining was visualized under a microscope (BX51, Olympus). Skin Culture C57BL/6 skin cultures were generated using the dorsal skin of newborn mice harvested on ice and transferred to culture inserts of a two-chamber tissue culture system containing a collagen membrane Costar Transwell (Corning Inc., Corning, N.Y., USA). These skins were cultured in Dulbecco’s Modified Eagle’s medium (Gibco, Life Technologies Corporation) with 10% fetal bovine serum (Gibco, Life Technologies Corporation), 200 mM L-glutamine (Gibco, Life Technologies Corporation), 100 U/ml penicillin, and 100 μg/ml streptomycin (Gibco, Life Technologies Corporation) at 37 ° C in an atmosphere of 5% CO2 and 95% air [Nakamura et al., 2003]. After skins were treated for 3 days with 0.1 M PBS (pH 7.2), 5 ng/ml recombinant human activin B (R&D Systems, Minneapolis, Minn., USA) or 10 ng/ml recombinant human activin B, they were immediately embedded in optimal cutting temperature medium (German Leica) for longitudinal cryosection of the hair follicle for AP activity staining (stages 1–4) and H&E staining. One slice was selected from every 10 sections, and 15 sections were selected. Images were captured using Image-Pro Plus software, and 15 photomicrographs (×200) were randomly selected from each group to estimate the number of hair follicles.  

Materials and Methods Mouse A total of 40 6- to 8-week-old and a total of 35 1-day-old male and female specific pathogen-free level C57BL/6 mice were provided by the Southern Medical University laboratory animal center (SCXK 2011-0015, No. 0107238). The skin of the C57BL/6 mice was homogeneous pink colored when all dorsal skin hair follicles were in the telogen stage, but the skin color changed from gray to black if all dorsal skin hair follicles were induced into the anagen development stage. All experimental procedures were in compliance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and were approved by the Bioethics Committee of Southern Medical University. Alkaline Phosphate Activity Staining Mice were anesthetized with an intraperitoneal injection of 10% chloral hydrate (w/v; 0.003 ml/g body mass) and dorsal skins were carefully removed. Alkaline phosphate (AP) activity of frozen

Activin B in Hair Follicles

 

Depilation-Induced Models C57BL/6 mice were anesthetized with an intraperitoneal injection of 10% chloral hydrate (Sigma; w/v; 0.003 ml/g body mass) or of 1% pentobarbital sodium (Sigma; w/v; 0.01 ml/g body mass). After shearing with curved scissors (area 3 × 2.5 cm), a honey and wax mixture (Mayllice, Italian CP-WAX Corporation) was applied to the dorsal skin of 7-week-old mice where all dorsal skin hair follicles were in the telogen stage, as evidenced by the homogeneous pink skin color. Following the removal of the honey/wax mixture

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b

Fig. 1. Hair follicle initiation was induced by activin B in cultured neonatal mouse skins. Cryosections (7 μm) of cultured neonatal mouse skins were stained with H&E (a–c). H&E staining indicated that a greater number of hair follicles were present in the activin B (Act B)-treated groups (b, c). The total number of hair follicles in the activin-B-treated groups compared to PBS control mice is reported as the mean ± SD (d). A p value 1/3 the hair bulb diameter (fig. 4a, a1, a2). The qualitative and quantitative

evaluation of hair follicles show that the average anagen stages of hair follicles in the 5- and 10-ng/ml activin B group are stage 4.38 and stage 4.42, i.e., significantly higher than those in the PBS and 50-ng/ml activin B groups, with stages 3.38 and stage 3.56 (table 2), respectively, and these results suggest that activin B shortened the time from anagen stage 1 to anagen stage 6. Anagen 6 and catagen 1 stage hair follicles cannot be distinguished by morphologic criteria observed with a light microscope. However, using the TUNEL method, hair follicles with more than two TUNEL+ apoptotic keratinocytes in the bulb are defined as catagen stage 1 hair

Activin B in Hair Follicles

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Table 2. Hair cycle score for the anagen hair follicles in the PBS and activin B groups 9 days after depilation

Group

PBS 5 ng/ml activin B 10 ng/ml activin B 50 ng/ml activin B

Anagen stage of hair follicles (total n = 50) anagen 1 anagen 2

anagen 3

anagen 4

anagen 5

anagen 6

hair cycle score

0 0 0 0

22 2 2 20

10 28 30 11

9 10 9 12

0 8 8 0

3.38 4.38* 4.42* 3.56

9 1 1 7

Anagen 1 = factor 1; anagen 2 = factor 2; anagen 3 = factor 3; anagen 4 = factor 4; anagen 5 = factor 5; anagen 6 = factor 6. * Mean significant differences compared with the PBS group.

Table 3. Hair cycle score for the catagen hair follicles in the PBS and activin B groups 22 days after depilation

Group

PBS 5 ng/ml activin B 10 ng/ml activin B 50 ng/ml activin B

Catagen stage of hair follicles (total n = 50) catagen 1 – 3

catagen 4

catagen 5

catagen 6

catagen 7

catagen 8

hair cycle score

0 0 0 0

4 5 4 3

9 7 9 8

22 20 19 20

15 18 17 17

0 0 1 2

5.95 6.02* 6.04* 6.14

Catagen 1 = factor 1; catagen 2 = factor 2; catagen 3 = factor 3; catagen 4 = factor 4; catagen 5 = factor 5; catagen 6 = factor 6; catagen 7 = factor 7; catagen 8 = factor 8. * Mean significant difference compared with the PBS group.

follicles [Paus et al., 1999; Rogers, 2004]. Seventeen days after debilitation, in the 5- and 10-ng/ml activin B groups (data not shown), no apoptosis was detected in the hair bulbs. Similarly, the PBS and 50-ng/ml activin B groups (data not shown) did not contain any apoptotic cells. However, most of the hair follicles in the dorsal skins in all of the treatment groups were in the catagen 6 and 7 stage 22 days after depilation, based on the presence of epithelial strands that were longer than the DP diameters (online suppl. fig. S1C). The qualitative and quantitative evaluation of hair follicles shows that the average catagen stages in the PBS, 5-, 10- and 50-ng/ml activin B groups were similar (5.95, 6.02, 6.04 and 6.14, respectively; table  3). The results suggest that there was no difference among the four groups concerning the hair follicle cycle. In combination, these results suggest that activin B was able to induce hair follicles to enter the anagen stage from the telogen stage and to maintained hair follicles in the anagen stage.

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Discussion

Hair follicles are the only organ in adults that undergo regular cycles of self-regeneration [Schneider et al., 2009]. Hair follicle morphogenesis and hair cycling are controlled by complex bidirectional ectodermal-mesenchymal interactions between epidermal keratinocytes and a specialized population of fibroblasts whose morphogenic properties can be induced, resulting in maturation of the hair follice into DP [Epifano and Dean, 2002; Nowak et al., 2008]. In rodents, initiation of hair follicles occurs at E14.5, with the first biological events involving basal keratinocytes that are induced by signals from the mesenchyme to form the basal substrate (e.g., the bud of a hair follicle) at the bottom of the epithelium [Guo et al., 1996; Ma et al., 2004]. During this process, a variety of cytokines and signaling pathways are involved, including TGF-β, epidermal growth factor (EGF), bone morphogenetic protein (BMP) and Wnt signaling pathways. Activin, a member of the TGF-β superfamily, as well as activin acJia /Zhang /Kong /Chen /Chen /Wang / Zhang /Lang /Zhang /Zhang  

 

 

 

 

 

 

 

 

 

ceptors and their binding protein follistatin also play an important role [Danilenko et al., 1996; Kang et al., 2010; Lefever et al., 2010]. For example, activin B, a homodimer subunit of activin, has been shown to stimulate the wound healing process [Wankell et al., 2001; Bamberger et al., 2005]. In the present study, the effect of activin B on the initiation of hair follicles was investigated. Our results demonstrate that in the presence of activin B, the number of hair follicles present in cultured neonatal mouse skin increases. Since the regeneration of hair follicles during wound repair shares a common process with initiation of hair follicles during the embryonic period [Ito et al., 2007], it is consistent that activin B was also found to increase the proliferation of hair follicle cells and to promote the regeneration of hair follicles during wound healing [Zhang et al., 2011]. Accordingly, the in vivo studies in the present work highlight the role of activin B in promoting initiation of neonatal mouse hair follicles and in mediating the maturation of hair follicles. Each hair follicle perpetually cycles through 3 stages: growth (anagen), involution (catagen) and rest (telogen). Hair follicles present in different areas of the body also produce hairs of different lengths, and the length is proportional to the duration of the anagen cycle [Danilenko et al., 1996]. For example, scalp hair follicles stay in the anagen stage between 2 and 8 years to produce long hairs, whereas eyebrow hair follicles remain in the anagen stage for only 2–3 months [Stenn and Paus, 2001]. Determining the molecular signals that orchestrate a follicle’s transition between these 3 stages is one of the key challenges in hair research. In the present study, 9 days after inducing new follicle growth due to depilation, anagen stage 4 hair follicles were found in the dorsal skins of the 5- and 10-ng/ml activin B groups. In contrast, hair follicles of the PBS control group and the 50-ng/ml activin B group were mostly in anagen stages 2 and 3. Cytokines play a biological role in a concentration-dependent manner, with 2 ng/ml of βEGF promoting cell proliferation and 10 ng/ ml of βEGF significantly promoting wound healing; however, the higher concentrations at 50 ng/ml show no further increase [Chan et al., 1997]. Similar findings are that the insulin-like growth factor at low concentrations promoted fibroblast migration and at a high concentration inhibited migration [Jann et al., 1999]. The study found that 5 and 10 ng/ml of activin B promotes the transition of hair follicles from the telogen stage to the anagen stage, but this role of 50 ng/ml of activin B was decreased. This is similar to our previous findings that 1 ng/ml of activin B slightly promoted keratinocyte migration, and 10 ng/ ml of activin B significantly promoted keratinocyte mi-

gration and wound healing, but 100 ng/ml of activin B inhibited keratinocyte migration [Li et al., 2008]. The reason for this phenomenon may be that when activin B plays a biological role in an exogenous, autocrine or paracrine manner, excessive activin B can be captured and swallowed into the cell by the follistatin in the extracellular matrix and is then digested. In the circulatory system, absorbed exogenous activin B and follistatin were combined into complexes and were then gradually degraded [Keutmann et al., 2004]. In other studies, overexpression of activin-βA was found to inhibit the entry of hair follicles into a catagen stage from an anagen stage due to the downregulation of BMP2 expression and the upregulation of a BMP2 inhibitor [Plikus et al., 2009]. Another molecule with an important role in hair follicle cycling is fibroblast growth factor 5, which extends the anagen stage of hair follicle growth and upregulates EGF receptors [Danilenko et al., 2009]. However, although activin B was found to induce hair follicles to enter the anagen stage, no apoptosis was detected in the hair bulbs of any of the treatment groups, and a subset of hair follicles in all groups were in the catagen stage by day 22 following depilation. These results suggest that activin B induces hair follicles to enter the anagen stage from the telogen stage and accelerates the process from anagen stage 1 to anagen stage 4 as well as maintaining hair follicles in anagen stage 6. Similarly, mice lacking fibroblast growth factor 5 have an extended anagen stage, with the hair follicle eventually entering the catagen stage [Lefever et al., 2010]. Estrogen and androgen play different roles in the hair follicle and hair growth cycle. Estrogen prevents the transition of mouse hair follicles from the telogen phase to the anagen phase and also extends the anagen phase [Chanda et al., 2000]. Androgen has different effects on different hair [Ting et al., 2005]. However, in this study, we found no significant difference between male and female mice in either of the groups. Two reasons could be provided: one may be the younger age of mice (7 or even 6 weeks old) with a relatively low level of hormones; the other reason is that activin B not only decreases androstenedione production from primary theca cells but also regulates the synthesis of estrogen [Bernard et al., 2006; Young et al., 2012]. This result may be due to the interaction among them; the relative mechanism in this progress has not yet been determined. Therefore, the results of the present study suggest that other signaling pathways are important for the induction of the anagen stage and they identified new approaches for regulating both the hair follicle cycle and hair follicle regeneration during wound healing.

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Acknowledgements This work was supported by the Natural Science Foundation of China (81171824, 81371509 and 81371719), the Guangdong Province University Talent Introduction of Special Funds (C1031118),

the Key Project of the Chinese Ministry of Education (21132), Major Breakthroughs in Key Areas and Projects of Guangdong and Hongkong (2011A011304001), Science and Technology Development Program of Guangzhou Municipality (7411832133935), and Guangzhou Science and Technology Projects (12C32121608).

References Bamberger, C., A. Schärer, M. Antsiferova, B. Tychsen, S. Pankow, M. Müller, T. Rülicke, R. Paus, S. Werner (2005) Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes. Am J Pathol 167: 733–747. Bernard, B.A. (2002) Hair biology: an update. Int J Cosmet Sci 24: 13–16. Bernard, D.J., K.B. Lee, M.M. Santos (2006) Activin B can signal through both ALK4 and ALK7 in gonadotrope cells. Reprod Biol Endocrinol 4: 52. Chan, B.P., K.M. Chan, N. Maffulli, S. Webb, K.K. Lee (1997) Effect of basic fibroblast growth factor: an in vitro study of tendon healing. Clin Orthop Relat Res 342: 239–247. Chanda, S., C.L. Robinette, J.F. Couse, R.C. Smart (2000) 17beta-estradiol and ICI-182780 regulate the hair follicle cycle in mice through an estrogen receptor-alpha pathway. Am J Physiol Endocrinol Metab 278: 202–210. Danilenko, D.M., B.D. Ring, G.F. Pierce (1996) Growth factors and cytokines in hair follicle development and cycling: recent insight from animal models and the potentials for clinical therapy. Mol Med Today 2: 460–467. Epifano, O., J. Dean (2002) Genetic control of early folliculogenesis in mice. Trends Endocrinol Metab 13: 169–173. Guo, L., L. Degenstein, E. Fuchs (1996) Keratinocyte growth factor is required for hair development but not for wound healing. Genes Dev 10: 165–175. Hansen, L., N. Alexander, M.E. Hogan, J.P. Sundberg, A. Dlugosz, D.W. Threadgill, T. Magnuson, S.H. Yuspa (1997) Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. Am J Pathol 150: 1959–1975. Iida, M., S. Ihara, T. Matsuzaki (2007) Hair cycledependent changes of alkaline phosphatase activity in the mesenchyme and epithelium in mouse vibrissal follicles. Dev Growth Differ 49: 185–195. Ito, M., Z. Yang, T. Andl, C. Cui, N. Kim, SE. Millar, G. Cotsarelis (2007) Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447: 316–320. Jann, H.W., L.E. Stein, D.A. Slater (1999) In vitro effects of epidermal growth factor or insulinlike growth factor on tenoblast migration on absorbable suture material. Vet Surg 28: 268– 278.

326

Kang, B.M., S.H. Shin, M.H. Kwack, H. Shin, J.W. Oh, J. Kim, C. Moon, C. Moon, J.C. Kim, M.K. Kim, Y.K. Sung (2010) Erythropoietin promotes hair shaft growth in cultured human hair follicles and modulates hair growth in mice. J Dermatol Sci 59: 86–90. Keutmann, H.T., A.L. Schneyer, Y. Sidis (2004) The role of follistatin domains in follistatin biological action. Mol Endocrinol 18: 228– 240. Krause, K., K. Foitzik (2006) Biology of the hair follicle: the basics. Semin Cutan Med Surg 25: 2–10. Lefever, T., E. Pedersen, A. Basse, R. Paus, F. Quondamatteo, A.C. Stanley, L. Langbein, X. Wu, J. Wehland, S. Lommel, C. Brakebusch (2010) N-WASP is a novel regulator of hairfollicle cycling that controls antiproliferative TGF{beta} pathways. J Cell Sci 123: 128–140. Li, Q.L., N.K. Xiao, L. Zhang (2008) The role of activin B in skin wound healing. J Trop Med 8: 543–546. Ma, D.R., E.N. Yang, S.T. Lee (2004) A review: the location, molecular characterisation and multipotency of hair follicle epidermal stem cells. Ann Acad Med Singapore 33: 784–788. Maurer, M., E. Fische, B. Handjiski, A. Barandi, J. Meingasser, R. Paus (1997a) Activated skin mast cells are involved in hair follicle regression (catagen). Lab Invest 77: 319–332. Maurer, M., B. Handjiski, R. Paus (1997b) Hair growth modulation by topical immunophilin ligands: induction of anagen, inhibition of massive catagen development, and relative protection from chemotherapy-induced alopecia. Am J Pathol 150: 1433–1441. McDowall, M., N.M. Edwards, A.B. Jahoda CA, Hynd PI (2008) The role of activins and follistatins in skin and hair follicle development and function. Cytokine Growth Factor Rev 19: 415–426. Müller-Röver, S., B. Handjiski, C. van der Veen, S. Eichmüller, K. Foitzik, I.A. McKay, K.S. Stenn, R. Paus (2001) A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol 117: 3–15.

Cells Tissues Organs 2013;198:318–326 DOI: 10.1159/000356304

Nakamura, M., M.M. Matzuk, B. Gerstmayer, A. Bosio, R. Lauster, Y. Miyachi, S. Werner, R. Paus (2003) Control of pelage hair follicle development and cycling by complex interactions between follistatin and activin. FASEB J 17: 497–499. Nowak, J.A., L. Polak, H.A. Pasolli, E. Fuchs (2008) Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell 3: 33–43. Paus, R., G. Cotsarelis (1999) The biology of hair follicle. N Engl J Med 341: 491–497. Paus, R., S. Müller-Röver, C. Van Der Veen, M. Maurer, S. Eichmüller, G. Ling, U. Hofmann, K. Foitzik, L. Mecklenburg, B. Handjiski (1999) A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. J Invest Dermatol 113: 523–532. Plikus, M.V., J. Mayer, D.D. Cruz, R.E. Baker, P.K. Maini, R. Maxson, C.M. Chuong (2009) Cyclic dermal BMP signaling regulates stem cell activation during hair regeneration. Nature 451: 340–344. Rogers, G.E. (2004) Hair follicle differentiation and regulation. Int J Dev Biol 48: 163–170. Schneider, M.R., R. Schmidt-Ullrich, R. Paus (2009) The hair follicle as a dynamic miniorgan. Curr Biol 19: R132–R142. Stenn, K.S., R. Paus (2001) Controls of hair follicle cycling. Physiol Rev 81: 449–494. Ting H.J., B.Y. Bao, C.L. Hsu, Y.F. Lee (2005) Androgen-receptor coregulators mediate the suppressive effect of androgen signals on vitamin D receptor activity. Endocrine 26: 1–9. Wankell, M., B. Munz, G. Hübner, W. Hans, E. Wolf, A. Goppelt, S. Werner (2001) Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis. EMBO J 20: 5361–5372. Werner, S., C. Alzheimer (2006) Roles of activin in tissue repair, fibrosis, and inflammatory disease. Cytokine Growth Factor Rev 17: 157– 171. Young, J.M., S. Henderson, C. Souza, H. Ludlow, N. Groome, A.S. McNeilly (2012) Activin B is produced early in antral follicular development and suppresses thecal androgen production. Reproduction 143: 637–650. Zhang, M., N.Y. Liu, X.E. Wang, Y.H. Chen, Q.L. Li, K.R. Lu, L. Sun, Q. Jia, L. Zhang, L. Zhang (2011) Activin B promotes epithelial wound healing in vivo through RhoA-JNK signaling pathway. PLoS One 6: e25143.

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

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...
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