miR-222调控多聚二磷酸腺苷核糖聚合酶-1在高糖致人肾系膜细胞外基质沉积中作用

Effect of miR-222 on the expression of ADP ribose polymerase-1 in extracellular matrix deposition of human renal mesangial cells induced by high glucose

目的探讨miR-222调控多聚二磷酸腺苷(ADP)核糖聚合酶-1(PARP-1)在高糖致人肾系膜细胞外基质沉积中的作用。方法体外培养人肾系膜细胞株(HMC),使用高糖(25 m M)处理人肾系膜细胞,部分细胞应用miR-222抑制物或miR-222模拟物进行干预处理,Western blot检测PARP-1及FN蛋白表达。结果高糖培养组HMC在24 h时miR-222的表达上调,较对照组上调2.53倍,两组间比较,差异有统计学意义(P<0.05)。高糖+miR-222模拟物组HMC转染miR-222模拟物,可有效下调其靶蛋白PARP-1的表达,是高糖培养组的52.2%;高糖+miR-222抑制物组HMC转染miR-222抑制物,可有效上调其靶蛋白PARP-1的表达,较高糖培养组升高17.3%,两组间比较,差异均有统计学意义(P<0.05)。HMC细胞转染miR-222模拟物,可有效下调FN的表达,是高糖培养组的60.9%;而转染miR-222抑制物可有效上调纤维连接蛋白(FN)的表达,较高糖培养组升高18.8%,两组间比较,差异均有统计学意义(P<0.05)。结论 miR-222可通过调控PARP-1促进HMC基质增生。

Objective To investigate the effect of miR222 on the expression of ADP ribose polymerase-1（ PARP-1） in extracellular matrix deposition of human renal mesangial cells induced by high glucose. Methods Human mesangial cells（ HRMC） were cultured in vitro,HRMC were treated with high glucose（ 25 m M）. Some cells were treated with mir-222 inhibitor or mir-222 analogue. The expression of PARP-1 and FN protein were detected by Western blot. Results The expression of mir-222 was up-regulated by HMC in the high-sugar culture group in 24 hours,which was 2. 53 times higher than that in the control group（ P〈0. 05）. In high glucose ＋ mir-222 analogue group,HMC transfected mir-222 analogue could effectively reduce the expression of its target protein PARP-1,which was52. 2% of the high-sugar culture group; in the high glucose ＋ mir-222 inhibitory group,HMC transfection of mir-222 inhibitor could effectively increase the expression of the target protein PARP-1,and the higher glucose culture group increased 17. 3%（ P〈0. 05）.HMC cells transfected with mir-222 analogue can effectively reduce the expression of FN,which was 60. 9% of the high-sugar culture group; transfection of mir-222 inhibitor could effectively increase the expression of fibrinolytic protein（ FN）,and the higher glucose culture group increased 18. 8%,and the difference between the two groups was statistically significant（ P〈0. 05）. Conclusion The miR-222 regulates mesangial cell proliferation by regulating PARP.