MicroRNA-325 alleviates myocardial fibrosis after myocardial infarction via downregulating GLI1

C.-C. Wang, B.-B. Shang, C.-W. Yang, Y.-F. Liu, X.-D. Li, S.-Y. Wang

Emergency Center, The Second Hospital of Dalian Medical University, Liaoning, China. tina2000wan@sohu.com

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• Cardiology

OBJECTIVE: To explore the role of microRNA-326 in myocardial fibrosis after myocardial infarction (MI) and its underlying mechanism.

MATERIALS AND METHODS: MI rat model was constructed via left anterior descending artery (LAD) ligation. Infarct tissues, infarct border zone tissues and remote zone tissues were harvested at postoperative 1st, 2nd, and 4th week, respectively. The mRNA levels of microRNA-325, collagen I, fibronectin, and transforming growth factor-β1 (TGF-β1) in the above tissues were detected by qRT-PCR (quantitative Real-time polymerase chain reaction). In vivo microRNA-325 upregulation was achieved by myocardial injection of microRNA-325 lentivirus. The effect of overexpressed microRNA-325 on overall survival (OS) and infarcted size was detected. Echocardiography was performed to evaluate rat cardiac function. Myocardial fibrosis affected by overexpressed microRNA-325 was evaluated via detecting α-SMA expression. Primary cardiac fibroblasts (CFs) were isolated and cultured in vitro. Cell counting kit-8 (CCK-8) and transwell assay were performed to evaluate the effect of microRNA-325 on regulating proliferative and migratory abilities of CFs. The regulatory role of microRNA-325 in GLI1 was verified by dual-luciferase reporter gene assay and Western blot.

RESULTS: MicroRNA-325 was downregulated in MI area, which was recovered to the normal level 4 weeks later. MicroRNA-325 overexpression could remarkably decrease the mortality and infarcted size of MI rats. Overexpressed microRNA-325 elevated LVEF and LVFS in MI rats. In vitro experiments demonstrated that microRNA-325 remarkably inhibited α-SMA expression, as well as proliferation and migration of CFs. Dual-luciferase reporter gene assay elucidated that microRNA-325 directly inhibited GLI1 expression.

CONCLUSIONS: Overexpressed microRNA-325 alleviates myocardial fibrosis after myocardial infarction via inhibiting GLI1 expression.

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