Valsartan ameliorates high glucose-induced peritoneal ï¬brosis by blocking mTORC1 signaling.
Exp Biol Med (Maywood)
; 245(11): 983-993, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32408765
ABSTRACT
IMPACT STATEMENT 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.
Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Soluções para Diálise
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Fibrose Peritoneal
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Valsartana
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Alvo Mecanístico do Complexo 1 de Rapamicina
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Glucose
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article