PKC{delta} as a regulator for TGF-{beta} stimulated connective tissue growth factor production in human hepatocarcinoma (HepG2) cells

In this study, the role of PKCδ in TGF-β1-mediated CTGF expression was investigated using HepG2 cells. TGF-β1 treatment specifically elevated PKCδ activation and CTGF expression. In contrast, blockade of PKCδ by the selective inhibitor, Rottlerin, or by siRNA knockdown significantly reduced TGF-β1-induced CTGF production. The regulatory mechanism was further demonstrated in HepG2 cells whereby TGF-β1-induced PKCδ activation negatively regulated nuclear levels of PPM1A through the RhoA/ROCK pathway. Moreover, we showed that both Smad signaling and the PKCδ pathway appeared to be stimulated by TGF-β1, in parallel. Time course assessments indicated that PKCδ signaling may have a function in maintaining nuclear phospho-Smads at maximal level. Our collective results demonstrated that PKCδ stimulated RhoA/ROCK activation resulted in a reduction of PPM1A phosphatase, thereby up-regulating Smad-dependent gene induction for extended periods. These findings indicated that PKCδ plays a critical role in TGF-β1-induced CTGF production in HepG2 cells.

Source: BJ Cell - August 29, 2013 Category: Biochemistry Authors: S Lee, J Kang, S Choi, O Kwon Tags: BJ Cell Source Type: research