BMP7 counteracts TGF beta1 induced endothelial-to-mesenchymal transition in viral cardiomyopathy and its potential mechanism

Abstract

Purpose: Cardiac fibrosis is the most important histological characteristics of viral cardiomyopathy and is associated with poor prognosis and therapeutic interventions. BMP7 is a member of TGF-β superfamily and was reported to counteract the effects of TGF-β1. This study was designed to evaluate whether BMP7 administration could reduce fibrosis induced by CVB3 infection and its potential mechanism. Methods: Viral myocarditis mice model was made and BMP7 was administrated to infected mice. Fourteen days after CVB3 infection, echocardiography, Sirius Red staining and hematoxylin-eosin (HE) were performed to describe the cardiac function and histological characteristics. Colocation of endothelial markers and mesenchymal markers were identified using confocal immunofluorescence staining. Western blot was performed to evaluate the TGF-β1/smad and Wnt/β-catenin signaling pathway. Results: A mice model of CVB3 myocarditis was made and BMP7 was administrated to CVB3-infected mice. Histological data demonstrated that BMP7 administration reduced inflammatory cells accumulation and cardiac fibrosis in response to CVB3 challenge. Echo data described cardiac dysfunction was recovered after BMP7 intervention. Double labeling of endothelial and mesenchymal markers showed BMP7-treated mice had significantly reduced the double-positive cells. Western blot described that TGF-β1/smad and Wnt/β-catenin signaling pathway was involved in this pathogenesis. Conclusions: BMP7 counteracts TGF-β1 induced endothelial-to-mesenchymal transition in viral cardiomyopathy through both TGF-β1/smad and Wnt/β-catenin signaling pathway. The research is supported by grant from the Health Joint-research Program of the National Natural Science Foundation of China and Canadian Institutes of Health Research (81010007) and National Natural Science Foundation of China (31070786)