摘要
自3.6亿年前陆生动物进化以来，一直存在着维持皮肤屏障的选择压力。这些动物获得了独特的表皮系统，具有角化，分层，鳞状上皮表面屏障。这个屏障可以防止脱水和微生物和毒素的进入。皮肤屏障以表皮角质层为中心，由角质层间脂质基质粘合的角质包膜组成。该屏障的多个组分通过谷氨酰胺转胺酶(TGM)进行交联，而角蛋白提供额外的机械强度。细胞紧密连接对于屏障的完整性也是至关重要的。GRHL转录因子在不同物种中调控被的形成和维持。GRHL3在胚胎发育期间对皮肤屏障的形成至关重要，而GRHL1在出生后维持皮肤屏障。这分别是通过Tgm1和Tgm5的转激活来实现的。除了屏障功能外，GRHL3在伤口修复和表皮肿瘤抑制中起关键作用。 In its former role, GRHL3 activates the planar cell polarity signalling pathway to mediate wound healing by providing directional migration cues. In squamous epithelium, GRHL3 regulates the balance between proliferation and differentiation, and its loss induces squamous cell carcinoma (SCC). In the skin, this is mediated through increased expression of MIR21, which reduces the expression levels of GRHL3 and its direct target, PTEN, leading to activation of the PI3K-AKT signalling pathway. These data position the GRHL family as master regulators of epidermal homeostasis across a vast gulf of evolutionary history.
| 原始语言 | 英语 |
|---|---|
| 页面(从) | 553年的今天,e152doi: 10.1111 / vde.12956 |
| 页数 | 15 |
| 杂志 | 兽医皮肤病 |
| 体积 | 32 |
| 问题数量 | 6 |
| 必须 | |
| 发布状态 | 发表,2021年12月 |