层流切应力诱导microRNA-101下调EZH2抑制血管新生

Down-regulation of EZH2 for antiangiogenesis by microRNA-101 as induced by laminar shear stress

目的探讨层流切应力调控microRNA-101(miR-101)及蛋白Zeste增强同源物2(EZH2)表达的机制,及其对血管内皮细胞功能的影响。方法以人脐静脉内皮细胞(ECs)为研究对象,使用层流切应力处理细胞,检测miR-101及EZH2的表达水平,并通过抑制或过表达miR-101和EZH2进一步研究其对内皮细胞血管新生的影响。结果层流切应力处理的内皮细胞与对照组相比,miR-101表达上调,EZH2表达下调,血管新生减少(P<0.05或0.01)。抑制内皮细胞中miR-101的表达可使EZH2蛋白水平升高(P<0.05)。在层流切应力处理的细胞中,抑制miR-101后EZH2表达未见下调,层流切应力无明显抑制血管新生作用(P>0.05)。结论层流切应力或可通过诱导miR-101下调EZH2的表达水平,抑制血管新生。

Objective To investigate the mechanism by which laminar flow shear stress regulates the expression of microRNA-101(miR-101)and the protein Zeste-enhanced homologue 2(EZH2),as well as the effect on the function of vascular endothelial cells.Methods Human umbilical vein endothelial cells(ECs)were selected as the study objects and treated flow shear stress to detect the expression levels of miR-101 and EZH2,and its effect on endothelial cell angiogenesis is further studied by inhibiting or overexpressing miR-101 and EZH2.Results Compared with the Control Group,the endothelial cells treated with laminar flow shear stress had upregulated miR-101 expression,downregulated EZH2 Expression,and reduced angiogenesis(P<0.05 or 0.01).Inhibition of miR-101 expression in endothelial cells increased the EZH2 protein level(P<0.05).In the endothelial cells treated with laminar flow shear stress,EZH2 expression was not downregulated after inhibition of miR-101 in endothelial cells,and laminar flow shear stress showed no significant antiangiogenesis effect(P>0.05).Conclusion Laminar flow shear stress may induce miR-101 to downregulate the EZH2 expression level,and thereby inhibiting angiogenesis.