Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Abstract

Background Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis. Methods The anti-fibrotic role of metformin was assessed in 50\xa0mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO 2 )-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-β1)-induced differentiated lung fibroblasts were used for in vitro models. Results At the concentration of 300\xa0mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO 2 -instilled mice at the early and late fibrotic stages. Besides, metformin (range 2–10\xa0mM) reversed SiO 2 -induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway. Conclusions In this study, we identified that metformin might be a potential drug for silicosis treatment.