MiRNA-1297 inhibits myocardial fibrosis by targeting ULK1

M.-L. Li, R.-N. Li, Y.-M. Ma, B. Jiang, Y.-J. Chen, W.-X. Hu, C.-L. Qv, Y.-J. Zhang, Y.-Y. Song, Y. Wang

Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, China. wywarrenw@hotmail.com

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• Cardiology

OBJECTIVE: The aim of this study was to explore the potential effect of miRNA-1297 on myocardial fibrosis (MF) and its underlying mechanism.

MATERIALS AND METHODS: MF model was established by cardiac perfusion of Angiotensin II (Ang-II) in mice. The primary myocardial fibroblasts were extracted from MF mice (Ang-II infusion group) and controls (sham group), respectively. The relative levels of miRNA-1297 and ULK1 in the in vivo and in vitro MF models were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, the protein expressions of fibrosis-related genes in MF mice and primary myocardial fibroblasts were determined by Western Blot. Subsequently, the Dual-Luciferase Reporter Gene Assay was applied to verify the downstream gene of miRNA-1297. In addition, a series of rescue experiments were conducted to elucidate the role of miRNA-1297/ULK1 in regulating MF.

RESULTS: Masson staining showed plenty of micro-vessels around myocardial tissues and significantly increased contents of intercellular collagen in Ang-II infusion group when compared with those in the sham group. Western blot results revealed that the protein expressions of Col1a1 and α-SMA were significantly upregulated in myocardial tissues of MF mice. QRT-PCR data illustrated that miRNA-1297 was remarkably downregulated in MF model. ULK1 was verified as the target gene of miRNA-1297, which was upregulated in the MF model. The overexpression of miRNA-1297 or the knockdown of ULK1 could downregulate the protein levels of Col1a1 and α-SMA in primary myocardial fibroblasts extracted from MF mice. Notably, ULK1 overexpression could reverse the regulatory effect of miRNA-1297 on MF.

CONCLUSIONS: MiRNA-1297 suppresses myocardial fibrosis via down-regulating ULK1.

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