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

Abstract

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.

Rho‐associated kinases are crucial for myofibroblast differentiation and production of extracellular matrix in scleroderma fibroblasts

“…Our findings are supported by the observation that Rock is required for TGF␤-induced epithelialmesenchymal transition in lens epithelial cells (27). Furthermore, treatment with the Rock inhibitor Y27632 has been shown to reduce fibrotic changes in a mouse model of unilateral urethral obstructive kidney disease (28).…”

RhoA/ROCK Signaling Regulates TGFβ-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through MRTF-A

“…In lens epithelial cells, TGFβ induces RhoA activation with a corresponding increase in actin stress fibers and focal adhesions (32). Further, RhoA/ROCK signaling has been implicated in TGFβ-induced αSMA expression in mouse lens epithelial cells (27); however, the mechanism by which RhoA/ROCK signaling is linked to the expression of EMT-related markers has not been fully defined.…”

“…Activated RhoA, bound to GTP, signals through its two effectors, Rho-associated coiled-coil-forming protein serine/threonine kinase (ROCK1 and 2) and mammalian diaphanous homologs (mDia1 and 2), which are both required for assembly of actin stress fibers and focal adhesions in the promotion of actomyosin contractile force generation (25). The involvement of RhoA signaling through ROCK in TGFβ-induced EMT has been demonstrated in a number of in vitro and in vivo animal systems (26)(27)(28)(29)(30)(31). In lens epithelial cells, TGFβ induces RhoA activation with a corresponding increase in actin stress fibers and focal adhesions (32).…”

RhoC is essential in TGF-β1 induced epithelial-mesenchymal transition in cervical cancer cells

“…A reduction in the expression of E-cadherin initiates a series of reactions which finally result in breakdown of the intercellular tight junctions between cells, allowing cells to gain movement capability (4). A previous study demonstrated that the expression level of E-cadherin was reduced in EMT (17).…”

“…In addition, EMT is characterized by alterations in the expression of a series of biomarkers, in particular, reduced E-cadherin and increased Vimentin expression levels. Ras homolog gene family, member C guanosine triphosphatase (RhoC GTPase) is an important member of the Rho-GTPase family, which regulates actin cytoskeleton reorganization during cellular motility, and actively participates in the EMT process (4)(5)(6). However, the role of RhoC in the process of EMT has remained to be elucidated.…”