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.
