Rho activation is required for transforming growth factor-β-induced epithelial-mesenchymal transition in lens epithelial cells
Rho activation is required for transforming growth factor-β-induced epithelial-mesenchymal transition in lens epithelial cells
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DOI：
10.1016/j.cellbi.2007.04.006
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发表时间：
2007-10-01
影响因子：
3.9
通讯作者：
Yoo, Jiyun
中科院分区：
文献类型：
--
作者：
Cho, Hee Jun;Yoo, Jiyun
晶状体上皮细胞在损伤后发生上皮-间充质转化(EMT)，与白内障摘除一样，导致晶状体囊膜纤维化。我们最近发现，转化生长因子-β诱导的晶状体上皮细胞内膜转化依赖于PI3激酶/Akt信号通路。在这份报告中，我们认为Smad3在转化生长因子-β诱导的EMT中是必要的，因为显性-负性Smad3的表达阻止了α-SMA的表达和形态变化。我们还发现，转化生长因子-β可引起Rho活性的双相改变，而Rho效应石的选择性抑制剂Y27632在体外和体内均能抑制转化生长因子-β诱导的EMT。最后我们证明了Smad3的激活和Rho信号的激活是相互独立的。以上结果提示，Rho/ROCK的激活与Smad3共同参与了转化生长因子-β诱导的晶状体上皮细胞EMT。(C)2007年国际细胞生物学联合会。(C)爱思唯尔有限公司出版。版权所有。
Lens epithelial cells undergo epithelial-mesenchymal transition (EMT) after injury as in cataract extraction, leading to fibrosis of the lens capsule. We have recently shown that TGF-beta-induced EMT in lens epithelial cells depends on PI3 kinase/Akt signal pathway. In this report, we suggest Smad3 is necessary for TGF-beta-induced EMT by showing that the expression of dominant-negative Smad3 blocks the expression of a-smooth muscle actin (alpha-SMA) and morphological changes. We also show that TGF-induces a biphasic change in Rho activity, and that Y27632, a selective inhibitor of Rho effector ROCK, inhibits TGF-beta-induced EMT in vitro and in vivo. We finally show that Smad3 activation and Rho signal activation is independent each other. All of these findings suggest that Rho/ROCK activation together with Smad3 is necessary for TGF-beta-induced EMT in lens epitheliat cells. (c) 2007 International Federation for Cell Biology. (c) Published by Elsevier Ltd. All rights reserved.