title: Down-regulation of microRNA-320 suppresses cardiomyocyte apoptosis and protects against myocardial ischemia and reperfusion injury by targeting IGF-1.
abstract: Insulin-like growth factor-1 (IGF-1) is an important regulator of cardiomyocyte homeostasis and cardiac structure, and the prosurvival and antiapoptotic effects of IGF-1 have been investigated. However, the effect of microRNA-320 (miR-320) in ischemia and reperfusion (I/R) by targeting IGF-1 is rarely discussed. We investigated the role of miR-320 in I/R injury. A total of 192 healthy female Wistar rats were divided into eight groups (n = 24). Rat heart I/R model was established. Hemodynamics, infarct size weight (ISW), heart function, and rat cardiomyocyte apoptosis were measured. Hypoxia-reoxygenation (H/R) in rat cardiomyocyte was used to simulate the I/R process. The mRNA levels of miR-320 and IGF-1, and proteins levels of IGF-1, IGF-1R, p-IGF-1R, p-ASK1, p-JNK, p-p38, Bcl-2, Bax and Caspase-3 were measured. In vivo inhibition of miR-320 expression significantly increased IGF-1 and IGF-1R mRNA levels, elevated the absolute values of SBP, DBP, MAP, ± dp/dtmax, LVEF and LVFS, decreased ISW, LVESD and LVEDd and the number of TUNEL positive cells, lowered the levels of p-ASK1, p-JNK, p-p38, Bax and Caspase-3 and increased expression of Bcl-2 compared to the I/R + NC group. Compared to H/R + NC group in vitro, miR-320 inhibition increased IGF-1 mRNA levels, inhibited cardiomyocyte apoptosis, down-regulated p-ASK, p-JNK, p-p38, Bax and Caspase-3 levels, and up-regulated Bcl-2 level. MiR-320 inhibition target elevated IGF-1 mRNA and protein levels, suppress early cardiomyocyte apoptosis of I/R, and inhibited ASK1-JNK/p38 pathway, which provides a new target for clinical study of I/R injury.
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Song
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Diao
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Shi
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Ji-Chang
authors.initials: JC
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Yang-Xue
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Yu
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006439:Hemodynamics; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism
chemical_list: C000602002:MIRN320 microRNA, rat; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D007334:Insulin-Like Growth Factor I; D053148:Caspase 3
keywords: apoptosis rate; cardiomyocytes; hypoxia-reoxygenation; ischemia-reperfusion; microRNA-320