Abstract
Cardiac fibrosis is a hallmark of cardiovascular diseases. Several studies have indicated that microRNAs (miRs) are associated with the development of cardiac fibrosis. However, to date, the underlying molecular mechanisms of miR-489 in cardiac fibrosis have not been studied. The present study investigated the biological function of miR-489 in isoproterenol (ISO)-induced cardiac fibrosis. It was observed that miR-489 was downregulated in the heart tissue and cardiac fibroblasts (CFs) obtained from rats with ISO-induced cardiac fibrosis, as compared with the levels in the control group. By contrast, the expression levels of histone deacetylase 2 (HDAC2), collagen I (Col1A1) and α-smooth muscle actin (α-SMA) were increased in the heart tissue and CFs obtained from ISO-treated rats compared with the control group. Furthermore, ISO-treated CFs were transfected with a miR-489 mimic, which resulted in decreased viability and differentiation of CFs compared with the control group. Bioinformatics analysis and a dual-luciferase reporter assay further revealed that HDAC2 is a downstream target of miR-489. Subsequently, a loss-of-function experiment demonstrated that depletion of HDAC2 decreased the expression levels of Col1A1 and α-SMA in CFs. Taken together, the results obtained in the present study revealed that the miR-489/HDAC2 signaling pathway may serve as a novel regulatory mechanism in ISO-induced cardiac fibrosis and may increase the understanding on cardiac fibrosis.