Activation of AMPK signalling by Metformin: Implication an important molecular mechanism for protecting against mice silicosis via inhibited endothelial cell-to-mesenchymal transition by regulating oxidative stress and apoptosis.

Inhalation of silica particles (SiO2) causes oxidative stress-induced inflammation and cell apoptosis, ultimately resulting in irreversible pulmonary fibrosis, Unfortunately, effective treatment or preventative measures have yet to be fully established. Metformin (Met), a relatively safe and effective medication for treating diabetes, may hold promise as protective agent against early-stage pulmonary fibrosis in mice through the activation of autophagy and inhibition of endothelial cell to mesenchymal transition (EndoMT). Here, we investigated whether Met could reduce silicosis in mice by regulating inflammation, oxidative stress, and apoptosis, and to identify the underlying protective effect on endothelial cells. First, through pathological observation, we found that 21 consecutive days of Met (100 mg/kg) administration is optimal against silicosis. Next, using haematoxylin-eosin and Masson's trichrome staining and immunoblotting, we found that Met effectively blunted the inflammatory response and collagen deposition at 56 days after exposure to SiO2. We also demonstrated that Met effectively activates AMPK signalling and markedly relieves oxidative stress, the mitochondrial apoptotic pathway and EndoMT induced by SiO2 exposure both in vivo and in vitro. Overall, Met can alleviate SiO2-induced pulmonary fibrosis by regulating oxidative stress and the mitochondrial apoptotic pathway. The current study provides a rationale for the clinical treatment of SiO2-induced pulmonary fibrosis.