Abstract: Objective To investigate the role of microRNA-21(miR-21) on cardiac fibroblast proliferation and differentiation in the mouse model of myocardial infarction. Method Male C57BL/6 mice underwent ligation of the left coronary artery to produce models of myocardial infarction (MI). Echocardiographic assessment and histological evaluation were performed after ligation. The expressing levels of miR-21 were measured by quantitative real-time PCR in the various myocardial tissues. The in vitro experiment was divided into control group, blank group and miR-21 minic group. In cardiac fibroblasts stably overexpressing miR-21 by transfection of miR-21 minic, proliferation was assessed by immunostaining for 5-ethynyl-2’-deoxyuridine (EdU). Western Blot was used to detect the expression of α-SMA and Smad7 in the cardiac fibroblasts. Results The expression of miR-21 was significantly increased in border area compared to remote areas in MI group than that of sham group (P<0.01). There was a higher expression of miR-21 in miR-21 minic group than those of control group and blank group (P<0.01). The EdU positive rate was significantly higher in miR-21 minic group than those of control group and blank group (P<0.01). Overexpression of miR-21 in cardiac fibroblasts increased α-SMA level, while Smad7 level, a target gene of miR-21, was significantly decreased. Conclusion Overexpression of miR-21 in cardiac fibroblasts disrupts TGF-β signaling pathway by reducing the expression of Smad7, which promotes the proliferation and differentiation of cardiac fibroblast, and finally regulates cardiac remodeling after myocardial infarction.

Key words: myocardial infarction, fibroblasts, cell proliferation, cell differentiation, microRNA-21