MicroRNA‑144 regulates angiotensin II‑induced cardiac fibroblast activation by targeting CREB

Liu,Zhi‑Yong; Lu,Mingjun; Liu,Jing; Wang,Zhao‑Ning; Wang,Wei‑Wei; Li,Yong; Song,Zhi‑Jing; Xu,Lingling; Liu,Qian; Li,Feng‑Hua

doi:10.3892/etm.2020.8901

MicroRNA‑144 regulates angiotensin II‑induced cardiac fibroblast activation by targeting CREB

Authors:
- Zhi‑Yong Liu
- Mingjun Lu
- Jing Liu
- Zhao‑Ning Wang
- Wei‑Wei Wang
- Yong Li
- Zhi‑Jing Song
- Lingling Xu
- Qian Liu
- Feng‑Hua Li
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Affiliations: Department of Cardiology, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Cardiology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China, Department of Endocrinology, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Orthopedics, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China
Published online on: June 17, 2020 https://doi.org/10.3892/etm.2020.8901
Pages: 2113-2121
Copyright: © Liu 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 involved in adverse cardiac remodeling and heart failure, which is the leading cause of deteriorated cardiac function. Accumulative evidence has elucidated that microRNAs (miRNAs) play important roles in the pathogenesis of cardiac fibrosis. However, the exact molecular mechanism underlying miR‑144 in cardiac fibrosis remains unknown. In the present study, a transverse aortic constriction (TAC) mouse model and angiotensin II (Ang II)‑induced cardiac fibroblasts (CFs) were constructed in order to investigate the expression levels of miR‑144. It was demonstrated that miR‑144 was significantly downregulated following pathological stimuli. CFs infected with miR‑144 mimics were then used to test the effect of miR‑144 on CF activation in vitro. The results revealed that overexpression of miR‑144 led to a dramatically decreased proliferation and migration ability in CFs, as well as the transformation from fibroblasts to myofibroblasts, which was characterized by the decreased expression of collagen‑I, collagen‑III, CTGF, fibronectin and α‑SMA. By contrast, such effects could be reversed by miR‑144 knockdown. Mechanistically, the bioinformatics analysis and luciferase reporter assay in the present study demonstrated that cAMP response element‑binding protein (CREB) was a direct target of miR‑144, and the expression of CREB was attenuated by miR‑144. The results of the present study demonstrated that miR‑144 played a key role in CF activation, partially by targeting CREB, which further suggested that the overexpression of miR‑144 may be a promising strategy for the treatment of cardiac fibrosis.

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