MicroRNA-214 exerts a Cardio-protective effect by inhibition of fibrosis

The miRNAs play important roles in regulating myocardial fibrosis. The purpose of this study was to determine the potential roles of microRNA-214 (miR-214) in cardiac fibrosis in vitro and in vivo. In vitro experiment, Ang II-induced cardiac fibroblasts (CFBs) are transfected with pre-miR-214, anti-miR-214 and their oligo controls. Gene expression was checked by Quantitative realtime-PCR (qRT-PCR) and western blotting. In the present experiment, compared with controls, expressions of collagen type I (COL I), collagen type III (COL III), transforming growth factor (TGF)-β1, and tissue inhibitors of metalloproteinase (TIMP)-1 were all increased, but matrix metalloproteinase (MMP)-1 was reduced in CFB by Ang II treatment at both mRNA and protein levels, and these alterations were found reversed by miR-214 transfection. In vivo, an anterior transmural acute myocardial infarction (AMI) was created by occlusion of the left anterior descending coronary artery after Ad-pre-miR-214, Ad-anti-miR-214 or Ad-GFP was delivered separately. Four weeks after AMI, protein contents of COL I, COL III and TGF-β1 in tissue from border area were found increased after AMI, but impaired by overexpression of miR-214. While the expression of MMP-1 was increased by miR-214 stimulation but decreased by miR-214 inhibition. These results suggested that miR-214 exerts cardio-protective effects by inhibition of fibrosis and the inhibitory effect involves TGF-β1 suppression and MMP-1/TIMP-1 regulation. Anat Rec, 299:1348-1357, 2016. © 2016 Wiley Periodicals, Inc.