title: Cardioprotective effect of miRNA-22 on hypoxia/reoxygenation induced cardiomyocyte injury in neonatal rats.
abstract: MicroRNAs (miRNAs) are implicated in the regulation of pathological and physiological processes in myocardial ischemia/reperfusion (MI/R). Recent studies have revealed that miR-22 might provide a potential cardioprotective effect on ischemic heart disease. However, the mechanism by which miR-22 prevents MI/R is still not fully clear. Here, we investigated the role of miR-22 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. MI/R was simulated in neonatal rat cardiomyocytes with 2h hypoxia followed by 4h reoxygenation. Prior to H/R, cells were transfected by Ad-miR-22 or Ad-scramble. It was revealed that H/R dramatically increased the release of CK and LDH, accompanied by a downregulation of miR-22 expression. Overexpression of miR-22 attenuated cardiomyocyte apoptosis and miR-22 target gene CREB binding protein (CBP) protein level, as determined by flow cytometry analysis and Western blot respectively. We further identified that miR-22 significantly inhibited CBP-related transcriptional factor AP-1 DNA binding activity under H/R. In addition, miR-22 could efficiently change Bcl-2/Bax ratio, and suppress the production of pro-inflammatory cytokines (TNF-α and IL-6) induced by H/R. In conclusion, these results suggest that miR-22 plays an important cardioprotective role partly via regulating CBP/AP-1 pathway to reduce cell apoptosis and inflammatory damage during MI/R injury.
authors.affiliation: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Optometry and Ophthalmology, Yichang Central People's Hospital, Yichang 443000, Hubei Province, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Jiawang
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China. Electronic address: yangjun@ctgu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002316:Cardiotonic Agents / Q000378:metabolism*; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; C580892:MIRN22 microRNA, rat; D008565:Membrane Proteins; D035683:MicroRNAs; C408142:Pag1 protein, rat; D010750:Phosphoproteins; D018808:Transcription Factor AP-1
keywords: Activator protein-1; Apoptosis; CREB binding protein; Inflammation; Ischemia/reperfusion injury; MicroRNA-22