Abstract: AIM: To observe the effect of metformin (Met) on the endothelial-mesenchymal transition (EMT) of rat alveolar epithelial type II cells and its mechanism. METHODS: The RLE-6TN cells were divided into 6 groups as follows: Control group; transforming growth factor-β1 (TGF-β1) group in which cells were incubated with TGF-β1 (5 ng/mL) for 48 h; TGF-β1+Met (1, 10, 100 μmol/L) group in which cells were pre-treated with Met (1, 10, 100 μmol/L) for 1 h, and then subjected to TGF-β1 (5 ng/mL) for 48 h; Met (100 μmol/L) group in which cells were incubated with Met (100 μmol/L) for 48 h. CCK-8 method was used to detect the cell proliferation. RT-PCR detected α-smooth muscle actin (α-SMA), vimentin, E-Cadherin, tight junction protein-1 (ZO-1), collagen I and collagen III mRNA expression. Western blotting was used to detect the protein expression of α-SMA, vimentin, E-Cadherin, ZO-1, collagen I, collagen III and levels of phosphorylated Smad2/3 and extracellular regulated protein kinases (ERK1/2). RESULTS: Metformin significantly inhibited the proliferation of RLE-6TN cells induced by TGF-β1 (P<0.05 or P<0.01), reduced the mRNA and protein expression of α-SMA, vimentin, collagen I, collagen III, and decreased the protein phosphorylation of Smad2/3 and ERK1/2 Level (P<0.05 or P<0.01) when compared with the TGF-β1 group. Conversely, metformin treatment increased the mRNA and protein expression of E-cadherin and ZO-1 (P<0.05 or P<0.01) compared with the TGF-β1 group. CONCLUSION: Metformin (10, 100 μmol/L) exhibits certain inhibitory effect on the EMT of RLE-6TN cells induced by TGF-β1, and its beneficial effects may be associated with the inhibition of the phosphorylation of Smad2/3 and ERK1/2.

Key words: metformin, pulmonary fibrosis, endothelial-mesenchymal transition, TGF-β1