Journal
CELLULAR SIGNALLING
Volume 25, Issue 1, Pages 159-167Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2012.09.001
Keywords
c-Ski; VSMC; Proliferation
Categories
Funding
- National Natural Science Foundation of China [81070229]
- Natural Science Foundation Project of Chongqing Science and Technology Commission, China [CSTC 2009BB5139]
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Proliferation of vascular smooth muscle cells (VSMCs) plays key roles in the progression of intimal hyperplasia, but the molecular mechanisms that trigger VSMC proliferation after vascular injury remain unclear, c-Ski, a co-repressor of transforming growth factor beta (TGF-beta)/Smad signaling, was detected to express in VSMC of rat artery. During the course of arterial VSMC proliferation induced by balloon injury in rat, the endogenous protein expressions of c-Ski decreased markedly in a time-dependent manner. In vivo c-Ski gene delivery was found to significantly suppress balloon injury-induced VSMC proliferation and neointima formation. Further investigation in A10 rat aortic smooth muscle cells demonstrated that overexpression of c-Ski gene inhibited TGF-beta 1 (1 ng/ml)-induced A10 cell proliferation while knockdown of c-Ski by RNAi enhanced the stimulatory effect of TGF-beta 1 on A10 cell growth. Western blot for signaling detection showed that suppression of Smad3 phosphorylation while stimulating p38 signaling associated with upregulation of cyclin-dependent kinase inhibitors p21 and p27 was responsible for the inhibitory effect of c-Ski on TGF beta 1-induced VSMC proliferation. These data suggest that the decrease of endogenous c-Ski expression is implicated in the progression of VSMC proliferation after arterial injury and c-Ski administration represents a promising role for treating intimal hyperplasia via inhibiting the proliferation of VSMC (C) 2012 Elsevier Inc. All rights reserved.
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