转化生长因子-β1及Sirt1/2参与高血压诱导的血管平滑肌细胞缝隙连接蛋白-43的表达及细胞增殖  

Involvement of TGF-β1 and Sirt1/2 in Connexin43 Expression and Proliferation of Vascular Smooth Muscle Cells Induced by Hypertension

作　　者：陈斯国[1] 吴宇奇[1] 李一帆[1] 黄凯[1] 姚庆苹[1] 沈宝荣[1] 严志强[1] 姜宗来[1] 

机构地区：[1]上海交通大学生命科学技术学院力学生物学与医学工程研究所,上海200240

出　　处：《生物物理学报》2012年第9期743-753,共11页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(10972141;10772120)~~

摘　　要：为探讨转化生长因子-β1及组蛋白去乙酰化酶Sirt1和Sirt2在高血压诱导的血管平滑肌细胞缝隙连接蛋白-43表达及细胞增殖中的作用,研究了腹主动脉窄缩诱导高血压大鼠和正常大鼠胸主动脉转化生长因子-β1、缝隙连接蛋白-43、Sirt1和Sirt2,以及细胞增殖标志蛋白增殖细胞核抗原表达的变化;观察Sirt1和Sirt2在转化生长因子-β1刺激大鼠VSMCs缝隙连接蛋白-43的表达及细胞增殖中的作用。结果显示,高血压大鼠胸主动脉的转化生长因子-β1、缝隙连接蛋白-43、TGF-β1、Sirt1和Sirt2的表达及细胞增殖较正常大鼠均明显升高;转化生长因子-β1促进了大鼠血管平滑肌细胞缝隙连接蛋白-43的表达和增殖,Sirt1与Sirt2的抑制剂Salermide有效抑制了转化生长因子-β1诱导的血管平滑肌细胞缝隙连接蛋白-43的表达与细胞增殖。结果表明,高血压通过上调转化生长因子-β1来诱导VSMCs缝隙连接蛋白-43的表达和细胞增殖,而Sirt1和Sirt2可能在其中起调控作用。This study investigated the effect and regulating mechanism of transforming growth factor-β1 （TGF-β1） and NAD＋-dependent protein deacetylases Sift1/2 on connexin43（Cx43） expression and proliferation in thoracic aorta of hypertension rats and vascular smooth muscle cells（VSMCs）. The models of hypertension were established by the coarctating abdomen aorta in SD rats. The expression of Cx43, TGF-β1, Sirtl/2 and PCNA in thoracic aorta of both hypertension and normal rats was examined by Western blotting. TGF-β1 recombinant protein and Sirtl/2 inhibitor salermide were used to treat rat VSMCs to identify the regulatory role and mechanism of TGF-β1 and Sirtl/2 on Cx43 expression and proliferation. Expression of Cx43, TGF-β1, Sirtl/2 and VSMC proliferation in hypertension rats were significantly increased. Treatment with TGF-β1 at concentration of 2, 5, 10 and 20 ng/mL increased the Cx43 expression in VSMCs in a dose-dependent manner. Cx43 expression showed a significant time-dependent manner in VSMCs treated with 10ng/mL TGF-β1. 50 μmol/L salermide inhibited the expression of Sirtl/2 and Cx43 induced by TGF-β1 in VSMCs. 50 μmol/L salermide could inhibit VSMC proliferation induced by TGF-β1. These results suggested that highly expression of Cx43 and proliferation of VSMCs in hypertension is regulated by TGF-β1 through induction of Sirtl/2 expression.

关 键 词：高血压 缝隙连接蛋白-43 细胞增殖 转化生长因子-Β1 Sirt1/2 

分 类 号：R318.0[医药卫生—生物医学工程]