Inhibition of TGF-βRI alleviates endothelial-mesenchymal transition of mitral valve damage due to rheumatic heart disease

Abstract

Abstract Background: Rheumatic heart disease (RHD) is an autoimmune disease caused by rheumatic fever following infection with Group A Streptococcus (GAS) that primarily affects the mitral valve, and our previous study has shown that endothelial-mesenchymal transition (EndMT) plays an important role in mitral valve damage due to RHD. TGF-β1 is an important profibrotic factor, but its role has not been explored in RHD. The current study is aimed to investigate the role of TGF-β1 in mitral valve damage due to RHD. Methods: RHD rats were established using inactivated GAS. Successful modelling of the RHD rat was verified in mitral valve pathology sections. Echocardiography and running test were used to detect the cardiac function of rats. And immunohistochemistry, RT-qPCR and Western blotting were used to detect activation of the TGF-β1/Smad signalling pathway and EndMT in mitral valve. Wounding healing and cell counting Kit-8 assay were conducted to figure out the function of TGF-β1 in vitro. Results: The TGF-β1/Smad signalling pathway was activated, and significant EndMT of the mitral valve occurred in RHD rats. And TGF-β type I receptor (TGF-βRI) inhibitor SB431542 inhibited the TGF-β1/Smad signalling pathway and EndMT of the mitral valve. Conclusion: EndMT was involved in mitral valve damage, and inhibition of TGF-βRI alleviated EndMT of mitral valve damage due to RHD.