Metformin attenuates angiotensin II-induced TGFβ1 expression by targeting hepatocyte nuclear factor-4-α.

ABSTRACT:

Background and purpose

Metformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. TGFβ1 is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects of metformin on TGFβ1 production induced by angiotensin II (AngII) and the underlying mechanisms.

Experimental approach

Wild-type and AMPKα2^-/- C57BL/6 mice were injected s.c. with metformin or saline and infused with AngII (3 mg·kg^-1 ·day^-1 ) for 7 days. Adult mouse cardiac fibroblasts (CFs) were isolated for in vitro experiments.

Key results

In CFs, metformin inhibited AngII-induced TGFβ1 expression via AMPK activation.

SUBMITTER: Chen R 

PROVIDER: S-EPMC5867023 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature