dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration.
dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration.
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DOI：
10.1016/j.stem.2015.07.008
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发表时间：
2015-08-06
期刊：
影响因子：
23.9
通讯作者：
Garza LA
中科院分区：
文献类型：
--
作者：
Nelson AM;Reddy SK;Ratliff TS;Hossain MZ;Katseff AS;Zhu AS;Chang E;Resnik SR;Page C;Kim D;Whittam AJ;Miller LS;Garza LA
皮肤和毛囊在受伤后再生--这一过程被称为创伤诱导毛发新生(WIHN)--是哺乳动物成年器官发生的罕见例子。因此，WIHN为破译哺乳动物再生的潜在机制提供了一个独特的模型系统。在这里，我们展示了从受损皮肤释放的dsRNA激活Toll样受体3(TLR3)及其下游效应因子IL6和STAT3来促进毛囊再生。相反，TLR3缺乏的动物无法启动WIHN。TLR3激活促进毛囊干细胞标记物的表达，并诱导核心毛发形态发生计划的元素，包括EDAR和Wnt和Shh途径。因此，我们的结果表明，dsRNA和TLR3将哺乳动物皮肤损伤的最早事件与再生联系起来，并提出了促进毛发新生的潜在治疗方法。
Regeneration of skin and hair follicles after wounding - a process known as wound-induced hair neogenesis (WIHN) - is a rare example of adult organogenesis in mammals. As such, WIHN provides a unique model system for deciphering mechanisms underlying mammalian regeneration. Here, we show that dsRNA, which is released from damaged skin, activates Toll-Like Receptor 3 (TLR3) and its downstream effectors IL6 and STAT3 to promote hair follicle regeneration. Conversely, TLR3-deficient animals fail to initiate WIHN. TLR3 activation promotes expression of hair follicle stem cell markers and induces elements of the core hair morphogenetic program, including EDAR and the Wnt and Shh pathways. Our results therefore show that dsRNA and TLR3 link the earliest events of mammalian skin wounding to regeneration and suggest potential therapeutic approaches for promoting hair neogenesis.