A new role for neurotrophins: involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control
A new role for neurotrophins: involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control
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DOI：
10.1096/fasebj.13.2.395
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发表时间：
1999-02-01
期刊：
影响因子：
4.8
通讯作者：
Paus, R
中科院分区：
文献类型：
--
作者：
Botchkarev, VA;Botchkareva, NV;Paus, R
神经营养因子发挥许多生物学作用，但不直接靶向神经元，包括体外调节角质形成细胞增殖和凋亡。在这里，我们利用小鼠毛囊的周期性生长和退化活动，探索皮肤中神经营养因子的潜在非神经元功能，并分析毛囊表达和BDNF，NT-4及其高亲和力受体TrkB的毛发生长调节功能。BDNF和NT-4 mRNA的皮肤表达具有显着的毛发周期依赖性，并在自发的、细胞凋亡驱动的毛囊退行（退行期）期间达到峰值。在退化期，BDNF的mRNA和免疫反应，以及NT-4的免疫反应，在退化的毛囊车厢中表达，而TrkB的mRNA和免疫反应中看到毛乳头成纤维细胞，上皮链，和烫发。BDNF或NT-4基因敲除小鼠表现出明显的退行期阻滞，而BDNF过表达小鼠表现出退行期加速和毛发长度明显缩短。最后，BDNF和NT-4在小鼠皮肤器官培养中加速退化期发育。总之，我们的数据表明，BDNF和NT-4在皮肤生理学中起着以前未被认识到的作用，作为毛发生长控制剂。因此，TrkB激动剂和拮抗剂值得探索作为新的毛发生长调节药物用于管理常见的毛发生长障碍。
Neurotrophins exert many biological effects not directly targeted at neurons, including modulation of keratinocyte proliferation and apoptosis in vitro. Here we exploit the cyclic growth and regression activity of the murine hair follicle to explore potential nonneuronal functions of neurotrophins in the skin, and analyze the follicular expression and hair growth-modulatory function of BDNF, NT-4, and their high-affinity receptor, TrkB. The cutaneous expression of BDNF and NT-4 mRNA was strikingly hair cycle dependent and peaked during the spontaneous, apoptosis-driven hair follicle regression (catagen). During catagen, BDNF mRNA and immunoreactivity, as well as NT-4-immunoreactivity, were expressed in the regressing hair follicle compartments, whereas TrkB mRNA and immunoreactivity were seen in dermal papilla fibroblasts, epithelial strand, and hair perm. BDNF or NT-4 knockout mice showed significant catagen retardation, whereas BDNF-overexpressing: mice dis played acceleration of catagen and significant shortening of hair length. Finally, BDNF and NT-4 accelerated catagen development in murine skin organ culture. Together, our data suggest that BDNF and NT-4 play a previously unrecognized role in skin physiology as agents of hair growth control. Thus, TrkB agonists and antagonists deserve exploration as novel hair growth-modulatory drugs for the management of common hair growth disorders.