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SM 22α regulates proliferation of vascular smooth muscle cells and inhibits neointimal formation after balloon injury in rats
Author(s) -
Dong Liuhua,
Wen Jinkun,
Miao Suibing,
Zheng Bin,
Han Mei
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb280
Subject(s) - vascular smooth muscle , gene knockdown , small interfering rna , platelet derived growth factor receptor , cell growth , microbiology and biotechnology , mapk/erk pathway , chemistry , signal transduction , cell cycle , cancer research , cell , biology , growth factor , receptor , endocrinology , apoptosis , rna , biochemistry , smooth muscle , gene
Smooth muscle 22 alpha (SM22α), a specific marker of contractile VSMCs, plays a role in inhibiting the phenotypic modulation of VSMCs. In this report, we found that overexpression of SM22α inhibited PDGF‐induced proliferation with concurrent blockade of the cell cycle progression in VSMCs. Despite of PDGF treatment, VSMCs infected with Ad‐SM22α were arrested in the G0/G1 phase, and showed increase in expression of the CDK inhibitors p21 and p27. Conversely, knockdown SM22α expression by specific small interfering RNA (siRNA) resulted in acceleration of cell cycle progression even if under serum deprivation. The evidences from an experiment in vivo showed that overexpression of SM22αinhibited neointimal formation induced by balloon injury. These findings suggest that SM22α abolishes pro‐proliferative signaling cascades and maintains the quiescent state of VSMCs. Furthermore, overexpression of SM22α resulted in a robust reduction in the activity of MEK/ERK1/2, but no change in the activity of JNK and p38 MAPK. Similarly, the activity of Raf was also reduced in SM22α‐overexpressed cells. The previous studies have demonstrated that Ras links PDGF receptor to Raf‐MEK/ERK1/2 pathway, mediating signal cascades in response to PDGF. We found that there was increase in binding of SM22α to Ras in SM22α‐overexpressed VSMCs, leading to negative regulation of Ras‐Raf‐MEK/ERK1/2 signaling pathway.