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Metformin inhibits high glucose‐induced mesangial cell proliferation, inflammation and ECM expression through the SIRT1‐FOXO1‐autophagy axis
Author(s) -
Xu Jiang,
Chen Yan,
Xing Yan,
Ye Shandong
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13120
Subject(s) - autophagy , metformin , foxo1 , inflammation , cell growth , chemistry , microbiology and biotechnology , mesangial cell , western blot , extracellular matrix , medicine , endocrinology , apoptosis , biology , biochemistry , protein kinase b , in vitro , insulin , gene
The aim of this study was to investigate the role of metformin in high glucose‐induced mesangial cell proliferation, inflammation and extracellular matrix (ECM) accumulation and to elucidate the underlying mechanism of metformin function. An MTT assay was used to examine rat mesangial cell (RMC) proliferation. The levels of TNF‐α, IL‐6 and TGF‐β in RMCs were determined by ELISA. The protein expression of fibronectin, collagen IV and autophagy‐related proteins (Beclin‐1, LC3‐I and LC3‐II) in RMCs was detected using western blot. Fluorescence microscopy analysis was carried out to evaluate RMC autophagy. Our results showed that high glucose‐induced RMC proliferation, inflammation and ECM expression, but these effects were markedly reduced by metformin. We confirmed that metformin suppressed high glucose‐induced RMC proliferation, inflammation and ECM expression via induction of autophagy. Mechanistic investigation demonstrated an axis of SIRT1‐FOXO1 in RMC autophagy. Our data indicated that metformin inhibits high glucose‐induced mesangial cell proliferation, inflammation and ECM expression through a SIRT1‐FOXO1‐autophagy axis.