MicroRNA-21 Regulates Cardiac Remodeling by Promoting Proliferation and Differentiation of Fibroblast after Myocardial Infarction

GUO Dong; ZHANG Minhong; XIAO Qingping; LIU Jianwen

doi:10.3969/j.issn.0253-9896.2014.05.013

Abstract：Objective To investigate the role of microRNA-21(miR-21) on cardiac fibroblast proliferation and dif-ferentiation in the mouse model of myocardial infarction. Methods The mouse model of myocardial infarction (MI) was es-tablished by ligation of the left coronary artery in male C57BL/6 mice(MI group). The echocardiographic assessment and his-tological evaluation were performed after ligation. The expression levels of miR-21 were measured by quantitative real-time PCR in the various myocardial tissues. The cardiac fibroblasts transfected with miR-21 mimic were over-expressed miR-21. The proliferation was assessed by immunostaining for 5-ethynyl-2’-deoxyuridine (EdU). Western blot assay was used to detect the expression ofα-SMA and Smad7 in the cardiac fibroblasts,and compared with control group and blank group. Results The expression of miR-21 was significantly increased in border area in MI group than that of sham group [(6.043 ± 0.231)×10-4 vs(1.620±0.451)×10-4,P<0.01]. There was a higher expression of miR-21 in miR-21 mimic group than that of control group and blank group [(4.839±0.705)×10-4 vs(1.143±0.064)×10-4 vs(1.017±0.201)×10-4,P<0.01]. The EdU positive rate was significantly higher in miR-21 mimic group than that of control group and blank group[(27.892±1.645)%vs(12.553 ± 1.227)% vs(13.946 ± 1.550)%,P<0.01]. The expression of α-SMA was significantly increased in miR-21 mimic group, while the expression of Smad7, a target gene of miR-21, was significantly decreased. Conclusion The over-expression of miR-21 in cardiac fibroblasts disrupts TGF-βsignaling pathway by reducing the expression of Smad7, which promotes the proliferation and differentiation of cardiac fibroblast, and finally regulates cardiac remodeling after myocardial infarction.