PI3K-ERK信号在胰岛素诱导的血管平滑肌细胞增殖中的作用

Inducing vascular smooth muscle cell proliferation by insulin involves in phosphatidylinositol 3-kinase and ERK1/2

目的:探讨胰岛素促血管平滑肌细胞增殖的分子机制。方法:原代培养的SD大鼠血管平滑肌细胞为研究对象,[3H]-TdR掺入实验观察胰岛素刺激后血管平滑肌细胞的增殖,免疫印迹分析PI3K-ERK信号在平滑肌细胞增殖中的作用。结果:胰岛素明显促进血管平滑肌细胞增殖,该作用呈现剂量依赖性关系,PI3K抑制剂LY294002、MAPK抑制剂PD98059可抑制胰岛素的促增殖作用,[3H]-TdR掺入分别下降48.8%、43.6%,抑制PI3K可下调胰岛素刺激的磷酸化ERK1/2蛋白表达和ERK活性,分别下降112%、127%。结论:PI3K-ERK1/2信号通路参与了胰岛素促平滑肌细胞增殖过程。

AIM： To investigate the effect of insulin on vascular smooth muscle cells （VSMCs） proliferation and to evaluate the intracellular signaling pathways involved. METHODS： VSMCs separated from Sprague - Dawley rats were used in this study. The proliferation of VSMCs induced by insulin was assayed by [ 3H ] - thymidin incorporation. The protein expression and activity of p - ERK1/2 were determined by immunblot and [ γ-32P] ATP incorporation. RESULTS： Insulin induced cell proliferation in a concentration - dependent manner. The proliferative effect of insulin on VSMCs was inhibited partly by LY294002 （48. 8% ）, an inhibitor of PI -3 kinase, and the ERK1/2 inhibitor PD98059 （43.6%）, respectively. Moreover, phosphorylation of ERK1/2 and activity of ERK1/2 induced by insulin were also inhibited partly by LY294002. CONCLUSION： PI -3 kinase and ERK1/2 are involved in insulin induced VSMCs proliferation.