Winge Mårten C G, Marinkovich M Peter
a Program in Epithelial Biology , Stanford University School of Medicine , Stanford , CA , USA.
b Dermatology Service , Veterans Affairs Medical Center , Palo Alto , CA , USA.
Small GTPases. 2019 May;10(3):163-168. doi: 10.1080/21541248.2016.1273861. Epub 2017 May 4.
The small GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1) plays a central role in skin homeostasis, including barrier function, wound healing and inflammatory responses. Psoriasis is a common skin disease characterized by deregulation of these functions, and affected skin exhibit keratinocyte hyperproliferation, inflammation and immune cell infiltration. Although psoriasis is often triggered by environmental stimulus, there is a strong genetic association with genes expressed in both immune cells and keratinocytes, of which several are linked to Rac1 signaling. Rac1 is highly active in human psoriatic lesional skin and keratinocytes, and keratinocyte-specific overexpression of an activated mutant of Rac1, Rac1, in a transgenic mouse model closely mimics the presentation of human psoriasis. Both Rac1 activation in keratinocytes and immune derived stimulus are required to drive psoriasiform signaling in transgenic mouse and human xenograft models of psoriasis. Therefore, understanding how increased Rac1 activation in psoriatic epidermis is regulated is central to understanding how the abnormal crosstalk between keratinocytes and immune cells is maintained.
小GTP酶Ras相关C3肉毒杆菌毒素底物1（RAC1）在皮肤稳态中起核心作用，包括屏障功能、伤口愈合和炎症反应。银屑病是一种常见的皮肤病，其特征是这些功能失调，受累皮肤表现出角质形成细胞过度增殖、炎症和免疫细胞浸润。虽然银屑病通常由环境刺激引发，但与免疫细胞和角质形成细胞中表达的基因有很强的遗传关联，其中一些与Rac1信号传导有关。Rac1在人类银屑病皮损皮肤和角质形成细胞中高度活跃，在转基因小鼠模型中角质形成细胞特异性过表达Rac1的活化突变体密切模拟了人类银屑病的表现。在转基因小鼠和银屑病人类异种移植模型中，角质形成细胞中的Rac1激活和免疫衍生刺激都是驱动银屑病样信号传导所必需的。因此，了解银屑病表皮中Rac1激活增加是如何被调节的，对于理解角质形成细胞和免疫细胞之间异常的相互作用是如何维持的至关重要。
