microRNA-29b Mediates the Antifibrotic Effect of Tanshinone IIA in Postinfarct Cardiac Remodeling
| Autor: | Hai-yu Li, Qiang-wei Shi, Ping Li, Shuai-bing Li, Luo-sha Zhao, Fan Yang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Cardiac fibrosis Myocardial Infarction Pharmacology Transfection Ventricular Function Left Rats Sprague-Dawley Transforming Growth Factor beta1 Downregulation and upregulation Fibrosis Internal medicine microRNA medicine Animals Smad3 Protein Ventricular remodeling Cells Cultured biology Dose-Response Relationship Drug Ventricular Remodeling business.industry Myocardium Transforming growth factor beta Recovery of Function Fibroblasts medicine.disease Up-Regulation Disease Models Animal MicroRNAs Endocrinology Abietanes biology.protein RNA Interference Collagen Signal transduction Cardiology and Cardiovascular Medicine business Transforming growth factor |
| Zdroj: | Journal of cardiovascular pharmacology. 65(5) |
| ISSN: | 1533-4023 |
| Popis: | BACKGROUND Tanshinone IIA (TSN) is one of the main components isolated from Danshen, which is widely used for the treatment of cardiovascular diseases. The transforming growth factor beta (TGF-β) signaling pathway and microRNA (miR)-29b play important roles in the progression of cardiac fibrosis and the modulation of cardiac fibroblast (CF) function. Our study investigated the role of miR-29b in the cardioprotective effects of TSN in postinfarct cardiac remodeling. METHODS AND RESULTS Echocardiography demonstrated that medium-dose TSN (TSN-M) and high-dose TSN (TSN-H) significantly inhibited postinfarct cardiac fibrosis and improved the impaired left ventricular function in rats subjected to acute myocardial infarction. Moreover, quantitative real-time polymerase chain reaction and Western blot demonstrated that TSN-M and TSN-H downregulated the expression of TGF-β1, Col1a1, Col3a1, and α-SMA but upregulated the expression of miR-29b. CFs treated with TSN showed inhibited TGF-β signaling pathway, downregulated expression of Col1a1, Col3a1, and α-SMA, and upregulated miR-29b expression in vitro. Furthermore, treatment with a miR-29b inhibitor dramatically inhibited these TSN-induced antifibrotic effects, suggesting that miR-29b may be responsible for the antifibrotic effects of TSN. In addition, treatment with Smad3 siRNA significantly inhibited miR-29b expression in CFs, which implies that Smad3 signaling promotes miR-29b expression on CFs. CONCLUSIONS TSN exerts antifibrotic effects in postinfarct cardiac fibrosis by upregulating the expression of miR-29b, which is mediated by the TGF-β-Smad3 signaling pathway. |
| Databáze: | OpenAIRE |
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