Review Volume 12, Issue 9 pp 8742—8759

Figure 1. Schematic of the mechanisms by which metformin protects against renal fibrosis. Metformin inhibits hypoxia-mediated renal fibrosis by inhibiting HIF1α stabilization via blocking the mitochondrial oxidative respiratory chain, reducing renal oxygen consumption; inhibits TGFβ1 generation and receptor binding to prevent TGFβ1-mediated renal fibrosis; promotes AMPK phosphorylation of ACC to increase FAO and slow renal fibrosis; inhibits hyperglycemia-induced expression of mi-R34a, which negatively regulates AMPK both directly and by downregulating SIRT1, reducing the pro-EMT factor EGR1. (HIF1α, hypoxia inducible factor 1α; TGFβ1, transforming growth factor β1; AMPK, AMP-activated kinase protein; ACC, acetyl-CoA carboxylase; FAO, fatty acid oxidation; miR-34a, microRNA-34a; EGR1, early growth response 1; EMT, epithelial-mesenchymal transition; OCT2, organic cation transporter 2).