Rho activation is required for transforming growth factor-beta-induced epithelial-mesenchymal transition in lens epithelial cells.
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.
Cho
Hee Jun
HJ
Department of Microbiology, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, South Korea.
Yoo
Jiyun
J
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D007908:Lens, Crystalline; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D008156:Luciferases; D020741:rho GTP-Binding Proteins