The role and mechanism of transforming growth factor beta 3 in human myocardial infarction-induced myocardial fibrosis.

ABSTRACT: Transforming growth factor beta (TGF?) plays a crucial role in tissue fibrosis. A number of studies have shown that TGF?3 significantly attenuated tissue fibrosis. However, the mechanism involved in this effect is poorly understood. In this study we found that the expression level of TGF?3 was higher in human myocardial infarction (MI) tissues than in normal tissues, and interestingly, it increased with the development of fibrosis post-myocardial infarction (post-MI). In vitro, human cardiac fibroblasts (CFs) were incubated with angiotensin II (Ang II) to mimic the ischaemic myocardium microenvironment and used to investigate the anti-fibrotic mechanism of TGF?3. Then, fibrosis-related proteins were detected by Western blot. It was revealed that TGF?3 up-regulation attenuated the proliferation, migration of human CFs and the expression of collagens, which are the main contributors to fibrosis, promoted the phenotype shift and the cross-linking of collagens. Importantly, the expression of collagens was higher in the si-smad7 groups than in the control groups, while silencing smad7 increased the phosphorylation level of the TGF?/smad signalling pathway. Collectively, these results indicated that TGF?3 inhibited fibrosis via the TGF?/smad signalling pathway, possibly attributable to the regulation of smad7, and that TGF?3 might serve as a potential therapeutic target for myocardial fibrosis post-MI.

SUBMITTER: Xue K 

PROVIDER: S-EPMC6533491 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature