HIF1α调控TRPC6通道在肾小球系膜细胞缺氧损伤中的分子机制

The Molecular Mechanism of HIF1α Regulating TRPC6 Channel in the Glomerular Mesangial Cells Hypoxic Injury

目的:探讨缺氧诱导因子-1α(hypoxia inducible factor 1α,HIF1α)和瞬时受体电位阳离子通道6(transient receptor potential cation channel 6,TRPC6)在人肾小球系膜细胞(mesangial cells,MC)缺氧损伤中的作用及机制。方法:用不同缺氧时间处理系膜细胞诱导细胞损伤,采用MTT还原法测定细胞存活率,Tunel法观察细胞凋亡情况,采用real-time PCR,Western-blot分析检测HIF1α及TRPC6的mRNA及蛋白含量变化。结果:缺氧可以诱导系膜细胞损伤,使系膜细胞HIF1α表达上调,TRPC6表达增加,导致细胞凋亡,应用HIF1α的抑制剂可以使TRPC6含量下调,细胞凋亡减轻。结论:HIF1α和TRPC6介导了缺氧诱导的系膜细胞凋亡。

Objective： To explore the role of hypoxia inducible factor 1α（HIF1α） and transient receptor potential cation channel 6（TRPC6） in human glomerular mesangial cells（MC） hypoxic injury. Methods： Mesangial cells were induced to cell damage with different hypoxic time. MTT method was used to determine cell damage,Tunel method was used to observe apoptosis,real-time PCR and western blot analysis were used to detect HIF1α and TRPC6 mRNA and protein expression. Results： Hypoxia can induce the damage of mesangial cells,increase the expression of HIF1α and TRPC6,lead to apoptosis. The application of HIF1α inhibitor can reduce TRPC6 expression and mesangial cell apoptosis. Conclusion： HIF1α and TRPC6 mediated the apoptosis of mesangial cells induced by hypoxia.