MiR-31 Downregulation Protects Against Cardiac Ischemia/Reperfusion Injury by Targeting Protein Kinase C Epsilon (PKCε) Directly.
BACKGROUND
Various miRNAs have been shown to participate in cardiac ischemia/reperfusion injury (I/R). miR-31 was identified as the most strikingly upregulated miRNA after acute myocardial infarction; therefore, the underlying role and mechanism of miR-31 in cardiac I/R was investigated.


METHODS
miR-31 expression was detected after cardiac I/R in mice. The cardioprotective effect of miR-31 downregulation was assessed in vitro and in vivo. The functional target gene and its downstream molecule were determined.


RESULTS
miR-31 expression increased after I/R. miR-31 downregulation increased cell viability and SOD activity and decreased LDH activity and MDA content in vitro. Additionally, miR-31 downregulation alleviated myocardial infarct size in vivo. PKCε was identified as the functional target gene of miR-31, and NFκB was identified as its downstream molecule that was involved in the miR-31-mediated cardioprotective effect.


CONCLUSIONS
miR-31 expression increased throughout the cardiac I/R process, and miR-31 downregulation induced a cardioprotective effect via a miR-31/PKCε/NFκB-dependent pathway.
Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Yongyi
Y
Wang
Min
M
Men
Wengang
W
Yang
Hui
H
Zheng
Song
S
Xue
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D015316:Genetic Therapy; D045022:Lactate Dehydrogenases / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D016328:NF-kappa B / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
D035683:MicroRNAs; C539917:Mirn31 microRNA, mouse; D016328:NF-kappa B; D045022:Lactate Dehydrogenases; D013482:Superoxide Dismutase; C497256:Prkce protein, mouse; D051744:Protein Kinase C-epsilon