We therefore examined the inhibitory mechanisms of metformin in TGF-β-induced myofibroblast differentiation of lung fibroblasts (LF), and also evaluated the anti-fibrotic role of metformin by using bleomycin (BLM)-induced lung fibrosis mouse models in relation to AMPK activation and NOX4 suppression. The gene discussed is NOX4; the disease is pulmonary fibrosis.