毛囊发育相关因子和信号通路研究进展
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摘要
毛囊发育具有周期性,其发育周期受多种调控。生物体内的一些生长因子如VEGF、HSP和EGF等可以通过直接或间接的方式影响毛囊的生长发育;一些如Wnt,BMP/TGFβ等相关信号通路也对毛囊周期等生命活动具有调控作用。笔者综述了与毛囊发育相关的生长因子、激素、活性蛋白以及信号通路的研究进展,并结合研究现状展望未来研究热点和应用前景。
The development of hair follicle(HF) is cyclical, and its cyclogeny is regulated by many factors.The growth factors such as VEGF, HSP and EGF can affect the growth and development of hair follicles in adirect or indirect way. Some signaling pathways, such as Wnt and BMP/TGF beta also regulate hair folliclecycle and other life activities. We summarized the research progress on the regulators for HF development,including growth factors, hormones, active proteins and signal pathways. Finally, we put forward the potentialresearch hotspot and application prospect of HF development.
The development of hair follicle(HF) is cyclical, and its cyclogeny is regulated by many factors.The growth factors such as VEGF, HSP and EGF can affect the growth and development of hair follicles in adirect or indirect way. Some signaling pathways, such as Wnt and BMP/TGF beta also regulate hair folliclecycle and other life activities. We summarized the research progress on the regulators for HF development,including growth factors, hormones, active proteins and signal pathways. Finally, we put forward the potentialresearch hotspot and application prospect of HF development.
引文
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[24] Mi H K, Ji S A, Jang J H, et al. SFRP2 augments Wnt/β-catenin signaling in cultured dermal papilla cells[J].Experimental Dermatology,2016,25(10):813-815.
[25]王乐乐,张燕军,杨坤,等.Wnt通路中部分基因在绒山羊胚胎皮肤毛囊中的表达[J].中国生物化学与分子生物学报,2016,32(1):99-106.
[26] Wang L C, Liu Z Y, Gambardella L, et al. Conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration[J].Journal of Investigative Dermatology,2000,114(5):901-908.
[27] Yamago G, Takata Y, Furuta I, et al. Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice[J].Archives of Dermatological Research,2001,293(9):435-441.
[28] Sadier A, Viriot L, Pantalacci S, et al. The ectodyspla-sin pathway:From disseasea to adaptations[J].Trends in Genetics,2014,30(1):24-31.
[29] Haara O, Fujimori S, Schmidt U R, et al. Ectodysplasin and Wnt pathways are required for salivary gland branching morphogcncsis[J].Development,2011,138(13):2681-2691.
[30] Tomann P, Paus R, Millar S E, et al. LHX2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth[J].Development,2016,143(9):1512-1522.
[31] Fujii M, Takeda K, Imanmra T, et a1. Roles of bone morphogenetic protein ype I receptors and Smad proteins in osteoblast and chondroblast differentiation[J].Molecular Biology of the Cell,1999,10(11):3801-3813.
[32] Kulessa H, Turk G, Hogan B L. Inhibition of Bmp signaling affects growth and differentiation in the anagen hair follicle[J].Embo Journal,2000,19(24):6664-6674.
[33] Qiu W, Lei M, Tang H, et al. Hoxc13 is a crucial regulator of murine hair cycle[J].Cell&Tissue Research,2016,364(1):149-158.
[34] Wang L, Siegenthaler J A, Dowell R D, et al. Foxc1 reinforces quiescence in self-renewing hair follicle stem cells[J].Science,2016,351(6273):613-617.
[35] Lay K, Kume T, Fuchs E. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential[J].Proceedings of the National Academy of Sciences,2016,113(11):E1506-E1515.
[36] Demehri S, Kopan R. Notch signaling in bulge stem cells is not required for selection of hair follicle fate[J].Development,2009,136(6):891-896.
[37] Goto A, Yamazaki N, Nogawa H. Characterization of FGF family growth factors concerning branching morphgenesis of mouse lung epithelium[J].Zoological Science,2014,31(5):267-273.
[38] Kiso M, Hamazaki TS, Itoh M, et al. Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive activity in murine vibrissal dermal papilla in vitro[J].Journal of Dermatological Science,2015,79(2):110-118.
[39] Kawano M, Komi-Kuramochi A, Asada M, et al. Comprehensive analysis of FGF and FGFR expression in skin:FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles[J].Journal of Investigative Dermatology,2005,124(5):877-885.
[40] Akilli,?ztürk,?zlem, et al. Gab1 and mapk signaling are essential in the hair cycle and fair follicle stem cell quiescence[J].Cell Reports,2015,13(3):561-572.
[41] Harel S, Higgins C A, Cerise J E, et al. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth[J].Science Advances,2015,1(9):1-12.
[2] Castexrizzi N, Lachgar S, Charvéron M, et al. Implication of VEGF, steroid hormones and neuropeptides in hair follicle cell responses[J].Annales De Dermatologie Et De Venereologie,2002,129(2):783-786.
[3] Su Y S, Fan Z X, Xiao S E, et al. Icariin promotes mouse hair follicle growth by increasing insulin-like growth factor 1 expression in dermal papillary cells[J].Clin Exp Dermatol,2017,42(3):287-294.
[4] Yu X J, Gao S Y, Cheng J Q, et al. Expression of HGF/c-met in the hair follicle growth cycle in mice[J].Acta Laboratorium Animalis Scientia Sinica,2015,4:406-409.
[5] Qi Y, Miao L, Lian X, et al. Therapeutic role of human hepatocyte growth factor(HGF)in treating hair loss[J].Peerj,2016,4(11):e2624.
[6]曹春花,高峰,王宏,等.不同浓度褪黑素刺激对内蒙古绒山羊毛囊干细胞增殖活性的影响[J].中国畜牧兽医,2016,43(2):438-443.
[7]杨雨江,孙丽敏,赵佳,等.Bax/Bcl-2基因在成年辽宁绒山羊皮肤次级毛囊表达及年周期变化规律[J].中国兽医学报,2016,2(36):326-335.
[8] Fang C, Li L and Li J. Conditional knockout in mice reveals the critical roles of Ppp2ca in epidermis development[J].International Journal of Molecular Sciences,2016,17(5):756-758.
[9] Adly M A, Assaf H A, Hussein M R. Expression of the heat shock protein-27 in the adult human scalp skin and hair follicle:hair cycledependent changes[J].Journal of the American Academy of Dermatology,2006,54(5):811-817.
[10] Xu W, Fan W, Yao K. Cyclosporine A stimulated hair growth from mouse vibrissae follicles in an organ culture model[J].Journal of Biomedical Research, 2012,26(5):372-380.
[11] Hibino T, Soma T, Horii I, et al. Activation of caspase-3 is involved in anagen-catagen transition of human hair follicles[J].Journal of Investigative Dermatology,1999,112(4):544-544.
[12] Kwack M H, Lee J H, Seo C H, et al. Dickkopf-1 is involved in dexamethasone-mediated hair follicle regression[J].Experimental Dermatology,2017,doi:10.1111/exd.13308.
[13] Xie L, Yang R, Liu S, et al. TR3 is preferentially expressed by bulge epithelial stem cells in human hair follicles[J].Laboratory Investigation,2016,96:81-88.
[14] Lei M, Gao X, Yang L, et al. Gsdma3 gene is needed for the induction of apoptosis-driven catagen during mouse hair follicle cycle[J]. Histochemistry and Cell Biology,2011,136(3):335-343.
[15] Búa S, Sotiropoulou P, Sgarlata C, et al. Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle[J].Cell Cycle,2015,14:24,3897-3907.
[16] Rosenquist T A, Martin G R. Fibroblast growth factor signaling in the hair growth cycle:expression of the fibroblast growth factor receptor and ligand genes in the murine hair follicle[J].Developmental Dynamics,1996,205(4):379-386.
[17]袁枫.FGF10和Spry4基因的克隆及在绵羊皮肤中的表达[D].新疆:新疆农业大学,2015.
[18] Andl T, Reddy ST, Gaddapara T,et al. WNT signals are required for the initiation of hair follicle development[J].Developmental Cell,2002,2(5):643-653.
[19] Kim B K, Yoon S K. Expression of sfrp2 is increased in catagen of hair follicles and inhibits keratinocyte proliferation[J].Annals of Dermatology,2014,26(1):79-87.
[20] Higgins C A, Petukhova L, Harel S, et al. FGF5 is a crucial regulator of hair length in humans[J].Proceedings of the National Academy of Sciences of the United States of America, 2014, 111(29):1064-10653.
[21] Xing Y, Ma X, Guo H, et al. Wnt5a Suppressesβ-catenin Signaling during Hair Follicle Regeneration[J]. International Journal of Medical Sciences,2016,13(8):603-610.
[22] Xiang M. Gene regulation by Wnt signaling pathway in the oriented differentiation of hair follicle stem cells[J].Journal of Tissue Engineering&Reconstructive Surgery,2011,7(5):290-294.
[23] Lin C M, Yuan Y P, Chen X C, et al. Expression of Wnt/β-catenin signaling, stem-cell markers and proliferating cell markers in rat whisker hair follicles[J].Journal of Molecular Histology, 2015, 46(3):233-240.
[24] Mi H K, Ji S A, Jang J H, et al. SFRP2 augments Wnt/β-catenin signaling in cultured dermal papilla cells[J].Experimental Dermatology,2016,25(10):813-815.
[25]王乐乐,张燕军,杨坤,等.Wnt通路中部分基因在绒山羊胚胎皮肤毛囊中的表达[J].中国生物化学与分子生物学报,2016,32(1):99-106.
[26] Wang L C, Liu Z Y, Gambardella L, et al. Conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration[J].Journal of Investigative Dermatology,2000,114(5):901-908.
[27] Yamago G, Takata Y, Furuta I, et al. Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice[J].Archives of Dermatological Research,2001,293(9):435-441.
[28] Sadier A, Viriot L, Pantalacci S, et al. The ectodyspla-sin pathway:From disseasea to adaptations[J].Trends in Genetics,2014,30(1):24-31.
[29] Haara O, Fujimori S, Schmidt U R, et al. Ectodysplasin and Wnt pathways are required for salivary gland branching morphogcncsis[J].Development,2011,138(13):2681-2691.
[30] Tomann P, Paus R, Millar S E, et al. LHX2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth[J].Development,2016,143(9):1512-1522.
[31] Fujii M, Takeda K, Imanmra T, et a1. Roles of bone morphogenetic protein ype I receptors and Smad proteins in osteoblast and chondroblast differentiation[J].Molecular Biology of the Cell,1999,10(11):3801-3813.
[32] Kulessa H, Turk G, Hogan B L. Inhibition of Bmp signaling affects growth and differentiation in the anagen hair follicle[J].Embo Journal,2000,19(24):6664-6674.
[33] Qiu W, Lei M, Tang H, et al. Hoxc13 is a crucial regulator of murine hair cycle[J].Cell&Tissue Research,2016,364(1):149-158.
[34] Wang L, Siegenthaler J A, Dowell R D, et al. Foxc1 reinforces quiescence in self-renewing hair follicle stem cells[J].Science,2016,351(6273):613-617.
[35] Lay K, Kume T, Fuchs E. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential[J].Proceedings of the National Academy of Sciences,2016,113(11):E1506-E1515.
[36] Demehri S, Kopan R. Notch signaling in bulge stem cells is not required for selection of hair follicle fate[J].Development,2009,136(6):891-896.
[37] Goto A, Yamazaki N, Nogawa H. Characterization of FGF family growth factors concerning branching morphgenesis of mouse lung epithelium[J].Zoological Science,2014,31(5):267-273.
[38] Kiso M, Hamazaki TS, Itoh M, et al. Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive activity in murine vibrissal dermal papilla in vitro[J].Journal of Dermatological Science,2015,79(2):110-118.
[39] Kawano M, Komi-Kuramochi A, Asada M, et al. Comprehensive analysis of FGF and FGFR expression in skin:FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles[J].Journal of Investigative Dermatology,2005,124(5):877-885.
[40] Akilli,?ztürk,?zlem, et al. Gab1 and mapk signaling are essential in the hair cycle and fair follicle stem cell quiescence[J].Cell Reports,2015,13(3):561-572.
[41] Harel S, Higgins C A, Cerise J E, et al. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth[J].Science Advances,2015,1(9):1-12.