School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
PLoS One. 2009 Dec 4;4(12):e8190. doi: 10.1371/journal.pone.0008190.
The human epidermis is comprised of several layers of specialized epithelial cells called keratinocytes. Normal homoeostasis of the epidermis requires that the balance between keratinocyte proliferation and terminal differentiation be tightly regulated. The mammalian serine/threonine kinases (ROCK1 and ROCK2) are well-characterised downstream effectors of the small GTPase RhoA. We have previously demonstrated that the RhoA/ROCK signalling pathway plays an important role in regulation of human keratinocyte proliferation and terminal differentiation. In this paper we addressed the question of which ROCK isoform was involved in regulation of keratinocyte differentiation.
We used RNAi to specifically knockdown ROCK1 or ROCK2 expression in cultured human keratinocytes. ROCK1 depletion results in decreased keratinocyte adhesion to fibronectin and an increase in terminal differentiation. Conversely, ROCK2 depletion results in increased keratinocyte adhesion to fibronectin and inhibits terminal differentiation.
These data suggest that ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation.
人类表皮由几层称为角质形成细胞的特化上皮细胞组成。表皮的正常同态需要严格调节角质形成细胞增殖和终末分化之间的平衡。哺乳动物丝氨酸/苏氨酸激酶（ROCK1 和 ROCK2）是小 GTP 酶 RhoA 的特征下游效应物。我们之前已经证明，RhoA/ROCK 信号通路在调节人角质形成细胞增殖和终末分化中起重要作用。在本文中，我们探讨了哪种 ROCK 同工酶参与调节角质形成细胞分化的问题。
我们使用 RNAi 特异性敲低培养的人角质形成细胞中的 ROCK1 或 ROCK2 表达。ROCK1 耗竭导致角质形成细胞对纤维连接蛋白的黏附减少，并增加终末分化。相反，ROCK2 耗竭导致角质形成细胞对纤维连接蛋白的黏附增加并抑制终末分化。
这些数据表明 ROCK1 和 ROCK2 在调节角质形成细胞黏附和终末分化中发挥不同的作用。
