Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte differentiation.

Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte differentiation.
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DOI:
10.1371/journal.pone.0008190
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发表时间:
2009-12-04
期刊:
影响因子:
3.7
通讯作者:
Hotchin NA
Hotchin NA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lock FE;Hotchin NA

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人类表皮由多层称为角质形成细胞的特殊上皮细胞组成。表皮的正常稳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 的下游效应器。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发挥着重要作用。在本文中,我们解决了哪种 ROCK 亚型参与角质形成细胞分化调节的问题。我们使用 RNAi 特异性敲低培养的人角质形成细胞中 ROCK1 或 ROCK2 的表达。 ROCK1 缺失会导致角质形成细胞对纤连蛋白的粘附减少,并导致终末分化增加。相反,ROCK2 缺失会导致角质形成细胞对纤连蛋白的粘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粘附和终末分化中发挥不同的作用。
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.
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