MicroRNA‑489 suppresses isoproterenol‑induced cardiac fibrosis by downregulating histone deacetylase 2

Yang,Xiaoyu; Yu,Tianhong; Zhang,Sheng

doi:10.3892/etm.2020.8470

MicroRNA‑489 suppresses isoproterenol‑induced cardiac fibrosis by downregulating histone deacetylase 2

Authors:
- Xiaoyu Yang
- Tianhong Yu
- Sheng Zhang
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Affiliations: Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, P.R. China
Published online on: January 23, 2020 https://doi.org/10.3892/etm.2020.8470
Pages: 2229-2235
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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