title: MiRNA-711-SP1-collagen-I pathway is involved in the anti-fibrotic effect of pioglitazone in myocardial infarction.
abstract: 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.
authors: 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, Beijing 100191, China.
authors: Na
authors: N
authors: Zhao
authors: Haiyi
authors: H
authors: Yu
authors: Haitao
authors: H
authors: Yu
authors: Min
authors: M
authors: Sun
authors: Youyi
authors: Y
authors: Zhang
authors: Ming
authors: M
authors: Xu
authors: Wei
authors: W
authors: Gao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D007004:Hypoglycemic Agents; C584825:MIRN711 microRNA, rat; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D045162:Thiazolidinediones; D000077205:Pioglitazone