Epidermal growth factor as a biologic switch in hair growth cycle
Epidermal growth factor as a biologic switch in hair growth cycle
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DOI：
10.1074/jbc.m212082200
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发表时间：
2003-07-11
影响因子：
4.8
通讯作者：
Chan, SY
中科院分区：
文献类型：
--
作者：
Mak, KKL;Chan, SY
毛发生长周期由三个阶段组成，称为生长期（生长）、退化期（退化）和休止期（静止）阶段。头发的这种周期性生长是由多种生长因子调节的。虽然正常表达的表皮生长因子及其受体（EGFR）的外根鞘下调与完成卵泡生长，在这里，我们表明，表皮生长因子在毛囊中的转基因小鼠的持续表达逮捕卵泡发育的最后阶段的形态发生。来自免疫沉淀和免疫印迹的数据显示，表皮生长因子信号通过表皮生长因子受体/ErbB 2异源二聚体在皮肤中。此外，局部应用tyrphostin AG 1478或AG 825，EGFR和ErbB 2的特异性抑制剂，分别完全抑制野生型小鼠的新毛发生长，但在转基因小鼠中不抑制。当转基因小鼠与具有较低EGFR激酶活性的wave-2小鼠杂交时，后代中的毛发表型被拯救。综上所述，这些数据表明EGFR信号传导对于毛发生长的启动是不可或缺的。另一方面，表皮生长因子的持续表达阻止进入退化期。我们认为表皮生长因子作为一种生物开关，在毛发生长周期的生长期开始和结束时在毛囊中打开和关闭，保护进入和退出生长期。
The hair growth cycle consists of three stages known as the anagen (growing), catagen (involution), and telogen (resting) phases. This cyclical growth of hair is regulated by a diversity of growth factors. Although normal expression of both epidermal growth factor and its receptor (EGFR) in the outer root sheath is down-regulated with the completion of follicular growth, here we show that continuous expression of epidermal growth factor in hair follicles of transgenic mice arrested follicular development at the final stage of morphogenesis. Data from immunoprecipitation and immunoblotting showed that epidermal growth factor signals through EGFR/ErbB2 heterodimers in skin. Furthermore, topical application of tyrphostin AG1478 or AG825, specific inhibitors of EGFR and ErbB2, respectively, completely inhibited new hair growth in wild type mice but not in transgenic mice. When the transgenic mice were crossed with waved-2 mice, which possess a lower kinase activity of EGFR, the hair phenotype was rescued in the offspring. Taken together, these data suggest that EGFR signaling is indispensable for the initiation of hair growth. On the other hand, continuous expression of epidermal growth factor prevents entry into the catagen phase. We propose that epidermal growth factor functions as a biologic switch that is turned on and off in hair follicles at the beginning and end of the anagen phase of the hair cycle, guarding the entry to and exit from the anagen phase.