MicroRNA-144 regulates angiotensin II-induced cardiac fibroblast activation by targeting CREB
Autor: | Mingjun Lu, Jing Liu, Qian Liu, Lingling Xu, Zhao‑Ning Wang, Liu Zhiyong, Zhi‑Jing Song, Feng‑Hua Li, Yong Li, Wei‑Wei Wang |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cardiac function curve Cancer Research Cardiac fibrosis myofibroblasts angiotensin II CREB 03 medical and health sciences 0302 clinical medicine Immunology and Microbiology (miscellaneous) cAMP response element-binding protein medicine cardiac fibroblasts Gene knockdown biology Oncogene Chemistry microRNA-144 General Medicine Articles medicine.disease Angiotensin II CTGF 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Cancer research Myofibroblast |
Zdroj: | Experimental and Therapeutic Medicine |
ISSN: | 1792-1015 1792-0981 |
Popis: | 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. |
Databáze: | OpenAIRE |
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