缬沙坦通过TGF-β1/Smad3信号通路调控足细胞血管生成素样蛋白4的表达  

Valsartan Regulates Angiopoietin-like Protein 4 Expression via TGF-β1/Smad3 Signaling Pathway in Podocytes

作　　者：肖红波[1] 郭岩岩 杨波 Xiao Hongbo;Guo Yanyan;Yang Bo(Department of Nephrology,Peking University Shenzhen Hospital,Shenzhen 518036,China;Institute of Urology,Shenzhen PKV-HKVST Medical Center,Shenzhen 518036,China)

机构地区：[1]北京大学深圳医院肾内科,深圳518036 [2]深圳北京大学香港科技大学医学中心泌尿外科研究所,深圳518036

出　　处：《华中科技大学学报（医学版）》2020年第5期545-549,555,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：深圳市“三名工程”项目(No.SZSM201812097);广东省自然科学基金资助项目(No.2018A030313669)。

摘　　要：目的探讨转化生长因子β1(TGF-β1)对人足细胞血管生成素样蛋白4(ANGPTL4)表达的影响,以及缬沙坦对这一作用的调控及相关机制。方法不同浓度TGF-β1(0、1、2.5、10 ng/mL)刺激常规培养的人足细胞系,刺激不同时间(12、24、48 h)后,RT-PCR和Western blot检测ANGPTL4的mRNA及蛋白表达情况;将人足细胞系分为4组:对照组、TGF-β1刺激组、Smad3抑制剂(SIS3)+TGF-β1组、缬沙坦+TGF-β1组,给予不同处理,检测ANGPTL4 mRNA及蛋白表达情况,以及Smad3和p-Smad3蛋白表达。结果TGF-β1刺激足细胞后,ANGPTL4 mRNA和蛋白表达水平呈剂量和时间依赖性升高;与TGF-β1单独刺激组比较,SIS3处理可显著抑制TGF-β1诱导的ANGPTL4 mRNA和蛋白表达水平的升高(均P<0.01),缬沙坦处理亦可显著抑制TGF-β1诱导的ANGPTL4 mRNA和蛋白表达以及p-Smad3/Smad3蛋白表达。结论TGF-β1/Smad3信号通路可调控足细胞ANGPTL4表达,缬沙坦可能通过TGF-β1/Smad3通路抑制足细胞ANGPTL4表达,从而发挥肾脏保护作用。Objective To evaluate the effect of transforming growth factorβ1(TGF-β1)on expression of angiopoietin-like protein 4(ANGPTL4)in human podocytes,and explore whether valsartan can regulate ANGPTL4 expression and its underlying mechanism.Methods Cultured human podocytes were stimulated with various doses of TGF-β1(0,1,2.5,10 ng/mL)for different time lengths(12,24,48 h),and RT-PCR and Western blotting were used to detect the levels of ANGPTL4 mRNA and protein.The cultured human podocytes were divided into 4 groups:control group,TGF-β1 group,Smad3 inhibitor(SIS3)+TGF-β1 group,valsartan+TGF-β1 group.And then the mRNA and protein levels of ANGPTL4 were detected,and the protein levels of Smad3 and p-Smad3 were also detected by Western blotting.Results TGF-β1 could promote the mRNA and protein levels of ANGPTL4 in human podocytes in a dose and time-dependent manner.Compared with TGF-β1 stimulation group,SIS3 treatment significantly inhibited TGF-β1-induced elevation of ANGPTL4 mRNA and protein levels(P<0.01).Moreover,valsartan treatment significantly inhibited TGF-β1-induced increase of ANGPTL4,p-Smad3 and Smad3.Conclusion TGF-β1/Smad3 signaling pathway can regulate podocyte ANGPTL4 expression,and valsartan might protect the kidney from injury by inhibiting podocytes ANGPTL4 expression through TGF-β1/Smad3 pathway.

关 键 词：血管生成素样蛋白4 足细胞 转化生长因子Β1 SMAD3 缬沙坦 

分 类 号：R965[医药卫生—药理学] R587.2[医药卫生—药学]