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

Transforming growth factor beta (TGF beta) plays a crucial role in tissue fibrosis. A number of studies have shown that TGF beta 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 beta 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 beta 3. Then, fibrosis-related proteins were detected by Western blot. It was revealed that TGF beta 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 beta/smad signalling pathway. Collectively, these results indicated that TGF beta 3 inhibited fibrosis via the TGF beta/smad signalling pathway, possibly attributable to the regulation of smad7, and that TGF beta 3 might serve as a potential therapeutic target for myocardial fibrosis post-MI.