Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

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 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO.sub.2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-[beta]1)-induced differentiated lung fibroblasts were used for in vitro models. Results At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO.sub.2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2-10 mM) reversed SiO.sub.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-[beta]1-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. Keywords: Occupational pulmonary fibrosis, Metformin, Epithelial-mesenchymal transition, Fibroblast-myofibroblast transition