title: MicroRNA-208b Alleviates Post-Infarction Myocardial Fibrosis in a Rat Model by Inhibiting GATA4.
abstract: BACKGROUND Myocardial infarction affects the health of many people. Post-infarction myocardial fibrosis has attracted much attention, but details of the mechanism remain elusive. In this study, the role of microRNA-208b (miR-208b) in modulating post-infarction myocardial fibrosis and the related mechanism were investigated. MATERIAL AND METHODS A rat model of myocardial infarction induced by ligating the left anterior descending artery was used to analyze the expression and roles of miR-208b by overexpression with the lentivirus vector of pre-miR-208b. Myocardial function was assessed and the expression of fibrosis-related factors type I collagen (COL1) and ACTA2 (alias αSMA) was detected. Myocardial fibroblasts isolated from newborn rats were transfected with luciferase reporter vectors containing wild-type or mutant Gata4 3' UTR to verify the relationship between Gata4 and miR-208b. We then transfected the specific small interference RNA of Gata4 to detect changes in COL1 and ACTA2. RESULTS miR-208b was down-regulated in hearts of model rats (P<0.01). Overexpressing miR-208b improved myocardial functions, such as reducing the infarction area (P<0.05) and promoting LVEF and LVFS (P<0.01), and inhibited COL1 and ACTA2 (P<0.01). Luciferase reporter assay proved Gata4 to be the direct target of miR-208b, with the target sequence in the 3'UTR. Inhibiting GATA4 resulted in the down-regulation of COL1 and ACTA2, suggesting that the role of miR-208b was achieved via regulating GATA4. CONCLUSIONS This study demonstrates the protective function of miR-208b via GATA4 in post-infarction myocardial fibrosis, providing a potential therapeutic target for treating myocardial fibrosis.
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China (mainland).
authors.forename: Chaoyuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China (mainland).
authors.forename: Qintao
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China (mainland).
authors.forename: Guobao
authors.initials: G
authors.lastname: Su
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China (mainland).
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China (mainland).
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China (mainland).
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D004719:Endomyocardial Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D050991:GATA4 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; D024042:Collagen Type I; D050991:GATA4 Transcription Factor; D035683:MicroRNAs; D034741:RNA, Small Interfering; C084365:Gata4 protein, rat; C569395:MIRN208 microRNA, rat; C498862:Acta2 protein, rat