Succinate receptor mediates Foxm1 expression to promote pulmonary fibrosis

Abstract:

Objective：To investigate the role and mechanism of succinate receptor（SUCNR1） in the occurrence and development of pulmonary fibrogenesis. Methods：A bleomycin-induced lung fiber model was constructed using SUCNR1 knockout（SUCNR1-/-） mice to observe the effects on pulmonary fibrosis. Transforming growth factor β1（TGF-β1） stimulated SUCNR1-/- primary lung fibrob－lasts cell proliferation was detected by MTT，and extracellular matrix（Collagen Ⅰ and α-SMA） was detected by western blot. The expression of forkhead box protein M1（Foxm1） in the lung tissue of each group of pulmonary fibrosis mice was detected. TGF-β1 and succinate stimulated primary lung fibroblasts were treated with Foxm1 inhibitor，and the effects on cell proliferation and extra－cellular matrix formation were observed. Results：The pulmonary fibrosis of SUCNR1-/- mice were significantly less than SUCNR1wt. The cells proliferation，and Collagen Ⅰ and α-SMA production was significantly reduced in SUCNR1-/- primary lung fibroblasts. Foxm1 was significantly elevated in the bleomycin-induced pulmonary fibrosis model，but significantly reduced in the SUCNR1-/- model. Inhibition of Foxm1 reduces TGF-β1 and succinate-induced lung fibroblast proliferation，Collagen Ⅰ and α-SMA generation. Conclusion：SUCNR1 participates in the development of pulmonary fibrosis，and its possible mechanism may be to activate lung fi－broblasts by promoting Foxm1 expression.