Ursolic acid attenuates diabetic mesangial cell injury by up-regulating autophagy via suppressing miRNA21-PTEN-Akt-mTOR pathway / 中华肾脏病杂志

ABSTRACT

Objective To investigate the underlying mechanism of ursolic acid in attenuating diabetic mesangial cells injury induced by high glucose (HG).Methods Rat glomerular mesangial cells were cultured in normal glucose,HG,HG with LY294002 and HG with ursolic acid.The cell proliferation and hypertrophy were detected by MTT and the ratio of total protein content to cell number.miRNA-21 was detected by quantitative real-time PCR.The PI3K-Akt-mTOR pathway,autophagy associated protein and collagen I were detected by Western blotting and quantitative realtime PCR.The autophagosomes were observed by electron microscope.Results Compared with normal control group,the cells exposed to HG showed up-regulating miRNA-21 expression(P ＜ 0.01),down-regulating PTEN protein and mRNA expression(P ＜ 0.01),up-regulating p85PI3K,phospho(p)-Akt,p-mTOR,p62/SQSTMI,collagen I expressions and down-regulating LC3II expression(P ＜ 0.01).Ursolic acid and LY294002 inhibited HG-induced mesangial cell hypertrophy and proliferation(P < 0.01),down -regulated the expressions of p85Pl3K,p-Akt,p-mTOR,p62/SQSTMI and collagen I and up-regulated the expression of LC3II(P ＜ 0.01).But LY294002 had no effect on the expression of miRNA-21 and PTEN.Ursolic acid down-regulated miRNA-21 expression(P ＜ 0.01),up-regulated PTEN protein and mRNA expression(P ＜ 0.01).Conclusion Ursolic acid may inhibit high glucose-induced mesangial cell miRNA-21 overexpression,up-regulate PTEN,inhibit the activation of PI3K-Akt-mTOR signaling pathway and the enhanced autophagy to reduce the accumulation of extracellular matrix and ameliorate cell hypertrophy and proliferation.