Role of miR-133a in regulating TGF-β1 signaling pathway in myocardial fibrosis after acute myocardial infarction in rats.

Abstract

The aim of this research was to explore the effect of microRNA-133a (miR-133a) on myocardial fibrosis and cardiac function after myocardial infarction in rats, and to investigate the possible regulatory mechanism. Myocardial infarction model was successfully established in rats by ligation of the left anterior descending coronary artery. After miR-133a overexpression in rats myocardium, cardiac function was examined by echocardiography. Meanwhile, the degree of myocardial fibrosis was detected by Masson staining. In addition, the expression of α-smooth muscle actin (α-SMA) in cardiomyocytes was detected by immunohistochemistry. Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to analyze the expression level of miR-133a in the junction of myocardial infarction. The mRNA expressions of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen type 1 (col 1), collagen type 3 (col 3) and α-SMA were measured by qRT-PCR as well. Furthermore, the protein levels of the above genes were detected by Western blotting. MiR-133a expression in the infarct border zone of myocardial tissue was significantly decreased on the 28th day after myocardial infarction surgery (p<0.05). In addition, up-regulation of miRNA-133a in myocardial tissue of rats with myocardial infarction could remarkably improve cardiac function and reduce collagen volume fraction. Furthermore, the mRNA and protein expression levels of TGF-β1, CTGF, col1, col3, α-SMA in myocardial tissue were obviously decreased after miRNA-133a up-regulation (p<0.001). Overexpression of miR-133a down-regulates the mRNA and protein levels of TGF-β1 and CTGF after myocardial infarction. Moreover, this may eventually reduce myocardial collagen deposition, inhibit myocardial fibrosis and improve cardiac function.