Cho Hee Jun, Yoo Jiyun
Department of Microbiology, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea.
Cell Biol Int. 2007 Oct;31(10):1225-30. doi: 10.1016/j.cellbi.2007.04.006. Epub 2007 Apr 25.
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 alpha-smooth muscle actin (alpha-SMA) and morphological changes. We also show that TGF-beta 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 epithelial cells.
晶状体上皮细胞在损伤后会发生上皮-间质转化（EMT），如在白内障摘除术中，这会导致晶状体囊膜纤维化。我们最近发现，转化生长因子-β（TGF-β）诱导的晶状体上皮细胞EMT依赖于磷脂酰肌醇-3激酶/蛋白激酶B（PI3激酶/Akt）信号通路。在本报告中，我们通过显示显性负性Smad3的表达阻断α-平滑肌肌动蛋白（α-SMA）的表达和形态变化，表明Smad3对于TGF-β诱导的EMT是必需的。我们还表明，TGF-β诱导Rho活性发生双相变化，并且Rho效应器ROCK的选择性抑制剂Y27632在体外和体内均抑制TGF-β诱导的EMT。我们最终表明，Smad3激活和Rho信号激活彼此独立。所有这些发现表明，Rho/ROCK激活与Smad3一起对于TGF-β诱导的晶状体上皮细胞EMT是必需的。
