Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang 050017, China.
Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):683-91. doi: 10.1161/ATVBAHA.109.200501. Epub 2010 Feb 5.
Vascular smooth muscle cells (VSMCs) can switch between differentiated and dedifferentiated phenotypes, and this phenotype switch is believed to be essential for repair of vascular injury. We studied the inhibitory effect of smooth muscle 22 alpha (SM22 alpha) on VSMC proliferation in vitro and in vivo and explored the potential molecular mechanisms of this effect.
By using coimmunoprecipitation and glutathione S-transferase pull-down assays, we have shown that SM22 alpha binds to Ras in SM22 alpha-overexpressed VSMCs in the presence or absence of platelet-derived growth factor-BB stimulation. SM22 alpha arrested cell cycle progression through segregation of Ras with Raf-1 and downregulation of the Raf-1-MEK1/2-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling cascade. The inhibitory effect of SM22 alpha on VSMC proliferation was verified in vivo. The infection of rat carotid arteries with recombinant adenovirus encoding SM22 alpha inhibited neointimal hyperplasia via suppression of the Raf-1-MEK1/2-extracellular signal-regulated kinase 1/2 signaling pathway.
These findings suggest that high expression of SM22 alpha inhibits cell proliferation via reduction of the response to mitogen stimuli in VSMCs and provide a novel mechanism by which VSMCs maintain their contractile phenotype and resist mitogenic stimuli in an SM22 alpha-dependent manner.
血管平滑肌细胞（VSMCs）可在分化和去分化表型之间转换，这种表型转换被认为是血管损伤修复所必需的。我们研究了平滑肌 22α（SM22α）在体外和体内对 VSMC 增殖的抑制作用，并探讨了这种作用的潜在分子机制。
通过共免疫沉淀和谷胱甘肽 S-转移酶下拉实验，我们已经表明，SM22α在血小板衍生生长因子-BB 刺激存在或不存在的情况下与 Ras 结合在 SM22α过表达的 VSMCs 中。SM22α 通过将 Ras 与 Raf-1 隔离和下调 Raf-1-MEK1/2-细胞外信号调节激酶 1/2 丝裂原活化蛋白激酶信号级联来阻止细胞周期进程。SM22α 对 VSMC 增殖的抑制作用在体内得到了验证。用编码 SM22α 的重组腺病毒感染大鼠颈动脉可抑制新生内膜增生，这是通过抑制 Raf-1-MEK1/2-细胞外信号调节激酶 1/2 信号通路实现的。
这些发现表明，SM22α 的高表达通过减少 VSMCs 对有丝分裂刺激的反应来抑制细胞增殖，并为 VSMCs 以 SM22α 依赖的方式维持其收缩表型和抵抗有丝分裂刺激提供了一种新的机制。
