miRNA-711-SP1-collagen-I pathway is involved in the anti-fibrotic effect of pioglitazone in myocardial infarction  

作　　者：ZHAO Na YU HaiYi YU HaiTao SUN Min ZHANG YouYi XU Ming GAO Wei 

机构地区：[1]Department of Cardiology,Peking University Third Hospital and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides,Ministry of Health,Key Laboratory of Molecular Cardiovascular Sciences,Ministry of Education

出　　处：《Science China(Life Sciences)》2013年第5期431-439,共9页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China (81100164,31271212,81070196,81030001);the Research Fund for the Doctoral Program of Higher Education (20100001110101,20110001120015);the Program for New Century Excellent Talents in University,the Beijing Talents Foundation

摘　　要：Although microRNAs （miRNAs） have been intensively studied in cardiac fibrosis, their roles in drug-mediated anti-fibrotic therapy are still unknown. Previously, Pioglitazone attenuated cardiac fibrosis and increased miR-711 experimentally. We aimed to explore the role and mechanism of miR-711 in pioglitazone-treated myocardial infarction in rats. Our results showed that pioglitazone significantly reduced collagen-I levels and increased miR-711 expression in myocardial infarction heart. Pioglitazone increased the expression of miR-711 in cardiac fibroblasts, and overexpression of miR-711 suppressed collagen-I levels in angiotensin II （Ang II）-treated or untreated cells. Transfection with antagomir-711 correspondingly abolished the pioglitazone-induced reduction in collagen-I levels. Bioinformatics analysis identified SP1, which directly promotes collagen-I synthesis, as the putative target of miR-711. This was confirmed by luciferase assay and western blot analysis. Additionally, increased SP1 expression was attenuated by pioglitazone in myocardial infarction heart. Furthermore, transfection of antago- mir-711 attenuated pioglitazone-reduced SP1 expression in cardiac fibroblasts with or without Ang II stimulation. We conclude that pioglitazone up-regulated miR-711 to reduce collagen-I levels in rats with myocardial infarction. The miR-711-SPl-collagen-I pathway may be involved in the anti-fibrotic effects of pioglitazone. Our findings may provide new strategies for miRNA-based anti-fibrotic drug research.Although microRNAs(miRNAs) have been intensively studied in cardiac fibrosis,their roles in drug-mediated anti-fibrotic therapy are still unknown.Previously,Pioglitazone attenuated cardiac fibrosis and increased miR-711 experimentally.We aimed to explore the role and mechanism of miR-711 in pioglitazone-treated myocardial infarction in rats.Our results showed that pioglitazone significantly reduced collagen-I levels and increased miR-711 expression in myocardial infarction heart.Pioglitazone increased the expression of miR-711 in cardiac fibroblasts,and overexpression of miR-711 suppressed collagen-I levels in angiotensin II(Ang II)-treated or untreated cells.Transfection with antagomir-711 correspondingly abolished the pioglitazone-induced reduction in collagen-I levels.Bioinformatics analysis identified SP1,which directly promotes collagen-I synthesis,as the putative target of miR-711.This was confirmed by luciferase assay and western blot analysis.Additionally,increased SP1 expression was attenuated by pioglitazone in myocardial infarction heart.Furthermore,transfection of antagomir-711 attenuated pioglitazone-reduced SP1 expression in cardiac fibroblasts with or without Ang II stimulation.We conclude that pioglitazone up-regulated miR-711 to reduce collagen-I levels in rats with myocardial infarction.The miR-711-SP1-collagen-I pathway may be involved in the anti-fibrotic effects of pioglitazone.Our findings may provide new strategies for miRNA-based anti-fibrotic drug research.

关 键 词：PIOGLITAZONE miR-711 cardiac fibrosis 

分 类 号：R542.22[医药卫生—心血管疾病]