The Role Of MiR-379 During Myocardial Fibrosis After Myocardial Infarction

Myocardial fibrosis caused by myocardial infarction(MI)is likely to cause the loss of heart function and arrhythmia.Myocardial fibrosis is characterized by activation,and enrichment of fibroblasts and consequent excessive deposition of extracellular matrix(ECM).The imbalance between synthesis and degradation of ECM is an important cause of poor ventricular remodeling after myocardial infarction.Therefore,the process of heart remodeling after MI is an important therapeutic target for post-MI management and heart failure.MicroRNAs(miRNAs)are involved in the regulation of cardiac embryo development,normal cardiovascular function,and pathological heart remodeling.For cardiovascular diseases and their complications,targeted therapy of miRNAs has great potential.In the previous study,our team constructed a ceRNA network related to myocardial infarction by analyzing the gene chip of myocardial infarction,including miR-379-5p.In order to clarify the role of miR-379-5p on myocardial infarction,we constructed a mouse model of myocardial infarction in this experiment.miR-379-5p was significantly up-regulated in a time-dependent manner after coronary artery ligation,and we hypothesized that miR-379-5p plays an important role in fibrosis after myocardial infarction.Upon detection,we found that the expression of miR-379-5p in CFs is markedly higher than which in cardiomyocytes.In cell experiments,TGF-β1 up-regulated the expression of miR-379-5p after stimulation of cardiac fibroblasts and up-regulated the mRNA expression level of fibrosis-related indicators.After transfection of miR-379-5p mimics into the CFs,the effect of TGF-β1-induced fibrosis was significantly inhibited.And the fibrosis level induced by TGF-β1 was further enhanced after transfection of miR-379-5p inhibitors.It was predicted that IL-11 is one of the target genes of miR-379-5p.Western Blot and qPCR results showed that IL-11 was up-regulated in the infarct border zone and infarct zone of myocardial infarction model mice.Transfection of miR-379-5p mimics into cardiac fibroblasts inhibited IL-11 expression,whereas up-regulation of IL-11 levels induced by TGF-β1 was more pronounced after transfection of miR-379-5p inhibitors.In addition,results showed that cardiac fibroblasts transfected with miR-379-5p mimics can inhibit its migration activity and proliferation level,and transfection of miR-379-5p inhibitors can promote its migration and proliferation level.Our results indicate that miR-379-5p exerts its anti-fibrotic role by directly inhibiting the expression of IL-11 in cardiac fibroblasts.