PI3K-Akt信号通路在胰岛素生长因子-1诱导平滑肌细胞中的作用

The effect of PI3K-Akt pathway in IGF-1 inducing proliferation of smooth muscle cell

目的比较胰岛素生长因子-1(IGF-1)对人脐静脉平滑肌细胞(HUVSMC)和脐动脉平滑肌细胞(HUASMC)增殖的影响并探讨其机制。方法采用人源HUVSMC和HUASMC进行研究,噻唑蓝(MTT)法检测IGF-1对两种细胞增殖的影响,并通过Westernblot技术检测IGF-1对两种细胞中PI3K-Akt信号通路的影响。结果不同浓度的IGF-1对HUVSMC和HUASMC的增殖都有明显的促进作用,但对HUVSMC的促增殖作用明显高于HUASMC。进一步检测PI3K-Akt信号通路,IGF-1可激活PI3K-Akt信号通路,并且IGF-1对HUVSMC的激活明显强于HUASMC。wortmannin(渥曼青霉素)明显抑制IGF-1对细胞增殖的促进作用。结论 IGF-1可明显促进平滑肌细胞增殖,并且在HUVSMC更为明显;IGF-1主要通过激活PI3K-Akt信号通路来促进平滑肌细胞的增殖。冠状动脉搭桥术(CABG)后静脉移植物比动脉移植物更容易发生内膜增生的原因可能就在于此。

Objective To investigate the effect of insulin-like growth factor-l（IGF-1 ） inducing proliferation of human umbilical vein smooth muscle cell（HUVSMC） and human umbilical artery smooth muscle cell（HUASMC） and its mechanism. Methods HUVSMC and HUASMC were cultured. Cell proliferation was measured using MTI＂ and phosphatidylinositol3-kinase（PI3K）-Akt（protein kinase B）signal path was measured by Western blot analysis. Results Different concentrations of IGF-1 can stimulate proliferation of HUVSMC and HUASMC but this proliferation was higher in HUVSMC than HUASMC. An upregulation of PI3K-Akt was observed in the HUVSMC in response to IGF-1 stimulation with lower effect in HUASMC. This effect was inhibited by wortmannin. Conclusions IGF-1 can promote the proliferation of SMC and this effect is greater in HUVSMC than HUASMC ;the activation of IGF-1 on the proliferation of SMC is mainly through PI3K-Akt. This may explain the greater propensity of the vein conduits than the atery to undergo intimal hyperplasia following CABG（ coronary artery bypass grafting）.