miR-138调节SIRT1p-STAT3通路抑制高糖诱导肾小球系膜细胞炎性反应及纤维化  

Inhibition Effect of miR-138 on Inflammatory Response and Fibrosis Induced by High Glucose in Glomerular Mesangial Cells by Regulating SIRT1p-STAT3 Pathway

作　　者：丁国明[1] 郑寿浩 戢晴 阮园[2] Ding Guoming;Zheng Shouhao;Ji Qing(Department of Nephrology First People′s Hospital of Taizhou City,Zhejiang 318020,China)

机构地区：[1]台州市第一人民医院肾内科,318020 [2]浙江医院内分泌科,杭州310013

出　　处：《医学研究杂志》2019年第8期100-104,114,共6页Journal of Medical Research

基　　金：浙江省医药卫生科技计划项目(2014KYB008)

摘　　要：目的探讨miR-138调节SIRT1p-STAT3通路抑制高糖诱导肾小球系膜细胞炎性反应及纤维化的机制。方法设NG组、NG+miRNA-138沉默组、NG+miRNA-138转染组、HG组、HG+miRNA-138沉默组、HG+miRNA-138转染组,以上各组每孔设6个平行样,培养72h,培养结束后,测定各组大鼠肾小球系膜细胞株miRNA138RNA水平以及SIRT1、P-STAT3、CTGF、ET-1、FN蛋白水平。结果HG组miRNA-138RNA、P-STAT3水平高于NG组,SIRT1水平低于NG组(P<0.05);NG+miRNA-138沉默组miRNA-138RNA、P-STAT3水平低于NG组,SIRT1水平高于NG组(P<0.05);NG+miRNA-138转染组miRNA-138RNA、P-STAT3水平高于NG组,SIRT1水平低于NG组(P<0.05);NG+miRNA-138转染组miRNA-138RNA、P-STAT3水平高于NG+miRNA-138沉默组,SIRT1水平低于NG+miRNA-138沉默组(P<0.05);HG+miRNA-138沉默组miRNA-138RNA、P-STAT3水平低于HG组,SIRT1水平高于HG组(P<0.05);HG+miRNA-138转染组miRNA-138RNA、P-STAT3水平高于HG组,SIRT1水平低于HG组(P<0.05);HG+miRNA-138转染组miRNA-138RNA、P-STAT3水平高于HG+miRNA-138沉默组(P<0.05);HG组TGF-β1、VEGF、CTGF、ET-1、FN水平高于NG组;NG+miRNA-138沉默组TGF-β1、VEGF、CTGF、ET-1、FN水平低于NG组(P<0.05);NG+miRNA-138转染组TGF-β1、VEGF、CTGF、ET-1、FN水平高于NG组(P<0.05);NG+miRNA-138转染组TGF-β1、VEGF、CTGF、ET-1、FN水平高于NG+miRNA-138沉默组(P<0.05);HG+miRNA-138沉默组TGF-β1、VEGF、CTGF、ET-1、FN水平低于HG组(P<0.05);HG+miRNA-138转染组TGF-β1、VEGF、CTGF、ET-1、FN水平高于HG组(P<0.05);HG+miRNA-138转染组TGF-β1、VEGF、水CTGF、ET-1、FN平高于HG+miRNA-138沉默组(P<0.05);miRNA-138与SIRT1呈负相关(P<0.01),SIRT1与P-STAT3呈负相关(P<0.05),P-STAT3与CTGF、ET-1、FN、TGF-β1、VEGF呈正相关(P<0.05)。结论miR-138促进高糖诱导的肾小球系膜细胞炎性反应及纤维化,其机制与抑制SIRT1引起的P-STAT3的磷酸化,导致TGF-β1、VEGF、CTGF、ET-1、FN高表达有关。Objective To investigate the inhibition effect and mechanism of miR-138 on inflammatory response and fibrosis induced by high glucose in glomerular mesangial cells by regulating SIRT1p-STAT3 pathway.Methods Cells were divided into NG group,NG+miRNA-138 silencing group,NG+miRNA-138 transfection group,HG group,HG+miRNA-138 silencing group and HG+miRNA-138 transfection group,and each group had 6 parallel samples per well.72h later,the levels of miRNA138 RNA,SIRT1,P-STAT3,CTGF,ET-1 and FN proteins in rat mesangial cells were determined.Results The level of miRNA-138 RNA and P-STAT3 in HG group was higher than that of the NG group ( P <0.05).The level of miRNA-138 RNA and P-STAT3 among HG groups ranked as HG+miRNA-138 transfection group > HG group > HG+miRNA-138 silencing group ( P <0.05).The level of miRNA-138 RNA and P-STAT3 among NG groups ranked as NG+miRNA-138 transfection group > NG group > NG+miRNA-138 silencing group ( P <0.05).The level of SIRT1 in HG group was lower than that of the NG group ( P <0.05).The level of miRNA-138 RNA and P-STAT3 among HG groups ranked as HG+miRNA-138 transfection group < HG group < HG+miRNA-138 silencing group ( P <0.05).The level of miRNA-138 RNA and P-STAT3 among NG groups ranked as NG+miRNA-138 transfection group <NG group < NG+miRNA-138 silencing group ( P <0.05).The levels of TGF-β1,VEGF,CTGF,ET-1 and FN in HG group was higher than that of the NG group ( P <0.05).The levels of TGF-β1,VEGF,CTGF,ET-1 and FN among HG groups ranked as HG+miRNA-138 transfection group > HG group > HG+miRNA-138 silencing group ( P <0.05).The levels of TGF-β1,VEGF,CTGF,ET-1 and FN among NG groups ranked as NG+miRNA-138 transfection group > NG group > NG+miRNA-138 silencing group ( P <0.05).miRNA-138 was negatively correlated with SIRT1 ( P <0.01),and SIRT1 was negatively correlated with P-STAT3 ( P <0.05).P-STAT3 was positively correlated with TGF-β1,VEGF,CTGF,ET-1 and FN levels ( P <0.05).Conclusion miR-138 promotes high glucose-induced glomerular mesangial cell inflammatory response and fibros

关 键 词：miR-138 SIRT1p-STAT3 高糖 肾小球系膜细胞 

分 类 号：R6[医药卫生—外科学]