Open AccessValsartan ameliorates high glucose-induced peritoneal fibrosis by blocking mTORC1 signaling
Author(s) -
Jing Liu,
Yuan Feng,
Chao Sun,
Wei Zhu,
Qingyan Zhang,
Bo Jin,
Qiuyuan Shao,
Yangyang Xia,
Pengfei Xu,
Miao Zhang,
Chunming Jiang
Publication year - 2020
Publication title -
experimental biology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 146
eISSN - 1535-3702
pISSN - 1535-3699
DOI - 10.1177/1535370220919364
Subject(s) - mtorc1 , peritoneal dialysis , extracellular matrix , peritoneum , fibrosis , endocrinology , valsartan , pi3k/akt/mtor pathway , signal transduction , medicine , chemistry , biochemistry , pathology , blood pressure
Our study provided new insight into the mechanism underlying the preservation of the peritoneum by valsartan. The results demonstrated that the mice receiving chronic high glucose (HG) peritoneal dialysis solution infusion showed a typical feature of peritoneal fibrosis (PF), as well as higher expression of α-smooth muscle actin (α-SMA) and collagen I. In vitro , HG increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly ameliorated these pathological changes. Interestingly, there was a parallel decrease in the activity of mammalian target of rapamycin complex 1 (mTORC1) and the protein expression levels of α-SMA and collagen I upon treatment with valsartan in vivo and in vitro . Moreover, the mTOR agonist MHY1485 reversed the downregulation of α-SMA and collagen I in vitro , even in the presence of valsartan. Altogether, our findings reported for the first time that valsartan exerts a protective effect against HG-induced PF by inhibiting the activity of the mTORC1 pathway.