高迁移率族蛋白B1在血管紧张素Ⅱ诱导的内皮-间充质转变过程中的作用

Role of high mobility group protein B1 in endothelial-mesenchymal transition induced by angiotensinⅡ

目的探讨高迁移率族蛋白B1(HMGB1)在血管紧张素Ⅱ(AngⅡ)诱导的内皮-间充质转变(EndMT)过程中的作用。方法将培养的人脐静脉内皮细胞(HUVECs)分为空白对照组、AngⅡ组、AngⅡ+siHMGB1组、AngⅡ+阴性对照组。各组给予相应处理5 d后,倒置显微镜观察内皮细胞形态的变化;Western blot检测HMGB1、CD31、VE-cadherin、成纤维细胞特异性蛋白1(FSP1)、α-平滑肌肌动蛋白(α-SMA)表达水平。结果与空白对照组相比,AngⅡ组细胞由鹅卵石样形态逐渐转变为梭形状态,HMGB1、FSP1、α-SMA表达水平均明显升高,CD31、VE-cadherin表达水平明显降低,差异有统计学意义(P<0.05)。与AngⅡ组比较,干扰HMGB1表达后细胞形态基本稳定,HMGB1、FSP1、α-SMA表达降低,CD31、VE-cadherin表达升高,差异有统计学意义(P<0.05)。AngⅡ组和AngⅡ+阴性对照组细胞形态均变为梭形状态,各蛋白表达变化趋势一致,差异无统计学意义(P>0.05)。结论HMGB1参与了AngⅡ诱导的内皮细胞EndMT过程。

Objective To investigate the role of high mobility group protein B1(HMGB1)in endothelial-mesenchymal transition(EndMT)induced by angiotensinⅡ(AngⅡ).Methods Cultured human umbilical vein endothelial cells(HUVECs)were randomly divided into four groups,as the blank control group,the AngⅡgroup,the AngⅡ+siHMGB1 group and the AngⅡ+negative control group.After 5 days of treatment,the morphological changes of endothelial cells were observed by inverted microscope.Western blot was used to test the expressions of HMGB1,CD31,VE-cadherin,fibroblast specific protein 1(FSP1)andα-smooth muscle actin(SMA)protein.Results Compared with the blank control group,the cells in the AngⅡgroup changed from cobblestone to shuttle morphology,and the expressions of HMGB1,FSP1 andα-SMA increased significantly,while the expressions of CD31 and VE-cadherin decreased.The differences were statistically significant(P<0.05).Compared with the AngⅡgroup,expression of HMGB1,FSP1,α-SMA decreased and CD31,VE-cadherin expression increased after interfering HMGB1 expression.The differences were statistically significant(P<0.05).The cell morphology all changed into shuttle morphology in the AngⅡgroup and the AngⅡ+negative control group,and the variation trends of protein expression were same,there was no significant difference(P>0.05).Conclusion HMGB1 is involved in EndMT induced by AngⅡin endothelial cells.