Rho activation is required for transforming growth factor-β-induced epithelial-mesenchymal transition in lens epithelial cells

摘要

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-β-induced EMT in lens epithelial cells depends on PI3 kinase/Akt signal pathway. In this report, we suggest Smad3 is necessary for TGF-β-induced EMT by showing that the expression of dominant-negative Smad3 blocks the expression of α-smooth muscle actin (α-SMA) and morphological changes. We also show that TGF-β induces a biphasic change in Rho activity, and that Y27632, a selective inhibitor of Rho effector ROCK, inhibits TGF-β-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-β-induced EMT in lens epithelial cells.