Smad7-induced β-catenin degradation alters epidermal appendage development
Smad7-induced β-catenin degradation alters epidermal appendage development
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DOI：
10.1016/j.devcel.2006.06.014
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发表时间：
2006-09-01
影响因子：
11.8
通讯作者：
Wang, Xiao-Jing
中科院分区：
文献类型：
--
作者：
Han, Gangwen;Li, Allen G.;Wang, Xiao-Jing
为了评估Smad信号是否影响皮肤发育，我们产生了转基因小鼠，其中Smad拮抗剂Smad 7在角质形成细胞（包括表皮干细胞）中诱导。Smad 7转基因诱导毛囊形态发生和分化，但加速皮脂腺形态发生。进一步的分析显示，独立于其在抗Smad信号传导中的作用，Smad 7结合β-连环蛋白并通过募集E3连接酶Smurf 2至Smad 7/β-连环蛋白复合物来诱导β-连环蛋白降解。因此，Wnt/β-连环蛋白信号在Smad 7转基因毛囊中被抑制。Smurf 2和Smad 7转基因的共表达加剧了Smad 7诱导的毛囊和皮脂腺异常。相反，当内源性Smad 7被敲低时，角质形成细胞表现出增加的β-连环蛋白和增强的Writ信号传导。我们的数据揭示了Smad 7拮抗Wnt/β-连环蛋白信号传导的机制，从而将皮肤分化程序从形成毛囊转移到皮脂腺。
To assess whether Smad signaling affects skin development, we generated transgenic mice in which a Smad antagonist, Smad7, was induced in keratinocytes, including epidermal stem cells. Smad7 transgene induction perturbed hair follicle morphogenesis and differentiation, but accelerated sebaceous gland morphogenesis. Further analysis revealed that independent of its role in anti-Smad signaling, Smad7 bound beta-catenin and induced beta-catenin degradation by recruiting an E3 ligase, Smurf2, to the Smad7/beta-catenin complex. Consequently, Wnt/beta-catenin signaling was suppressed in Smad7 transgenic hair follicles. Co-expression of the Smurf2 and Smad7 transgenes exacerbated Smad7-induced abnormalities in hair follicles and sebaceous glands. Conversely, when endogenous Smad7 was knocked down, keratinocytes exhibited increased beta-catenin protein and enhanced Writ signaling. Our data reveal a mechanism for Smad7 in antagonizing Wnt/beta-catenin signaling, thereby shifting the skin differentiation program from forming hair follicles to sebaceous glands.