miR-7a/b attenuates post-myocardial infarction remodeling and protects H9c2 cardiomyoblast against hypoxia-induced apoptosis involving Sp1 and PARP-1

miRs (microRNAs, miRNAs) intricately regulate physiological and pathological processes. Although miR-7a/b protects against cardiomyocyte injury in ischemia/reperfusion injury, the function of miR-7a/b in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Here, we sought to invest...

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Published in:Scientific reports 2016-07, Vol.6 (1), p.29082-29082, Article 29082
Main Authors: Li, Rui, Geng, Hai-hua, Xiao, Jie, Qin, Xiao-teng, Wang, Fu, Xing, Jun-hui, Xia, Yan-fei, Mao, Yang, Liang, Jing-wen, Ji, Xiao-ping
Format: Article
Language:English
Subjects:
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Adenosine diphosphate
Apoptosis
Cardiomyocytes
Collagen
Hazardous materials
Heart attacks
Heart failure
Humanities and Social Sciences
Hypoxia
Laboratory animals
MicroRNAs
multidisciplinary
Myocardial infarction
Science
Ultrasonic imaging
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Summary:miRs (microRNAs, miRNAs) intricately regulate physiological and pathological processes. Although miR-7a/b protects against cardiomyocyte injury in ischemia/reperfusion injury, the function of miR-7a/b in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Here, we sought to investigate the function of miR-7a/b in post-MI remodeling in a mouse model and to determine the underlying mechanisms involved. miR-7a/b overexpression improved cardiac function, attenuated cardiac remodeling and reduced fibrosis and apoptosis, whereas miR-7a/b silencing caused the opposite effects. Furthermore, miR-7a/b overexpression suppressed specific protein 1 (Sp1) and poly (ADP-ribose) polymerase (PARP-1) expression both in vivo and in vitro and a luciferase reporter activity assay showed that miR-7a/b could directly bind to Sp1. Mithramycin, an inhibitor of the DNA binding activity of Sp1, effectively repressed PARP-1 and caspase-3, whereas knocking down miR-7a/b partially counteracted these beneficial effects. Additionally, an immunoprecipitation assay indicated that hypoxia triggered activation of the binding activity of Sp1 to the promoters of PARP-1 and caspase-3, which is abrogated by miR-7a/b. In summary, these findings identified miR-7a/b as protectors of cardiac remodeling and hypoxia-induced injury in H9c2 cardiomyoblasts involving Sp1 and PARP-1.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep29082