MIAT Is a Pro-fibrotic Long Non-coding RNA Governing Cardiac Fibrosis in Post-infarct Myocardium
| Autor: | Yin Yuan, Xuefeng Qu, Ming Gao, Ti Yang, Yue Du, You Shu, Baofeng Yang, Fei Sun, Zhiguo Wang, Shenjian Luo, Yanjie Lu, Wenfeng Chu, Linfeng Zhan, Zhenwei Pan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cardiac function curve Cell Survival Cardiac fibrosis Myocardial Infarction 030204 cardiovascular system & hematology Article Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Fibrosis microRNA medicine Animals Myocardial infarction RNA Small Interfering Cell Proliferation Gene knockdown Multidisciplinary business.industry Myocardium Fibroblasts medicine.disease Angiotensin II Disease Models Animal MicroRNAs 030104 developmental biology Gene Expression Regulation Echocardiography Gene Knockdown Techniques Heart Function Tests Cancer research RNA Long Noncoding Collagen business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | A long non-coding RNA (lncRNA), named myocardial infarction associated transcript (MIAT), has been documented to confer risk of myocardial infarction (MI). The aim of this study is to elucidate the pathophysiological role of MIAT in regulation of cardiac fibrosis. In a mouse model of MI, we found that MIAT was remarkably up-regulated, which was accompanied by cardiac interstitial fibrosis. MIAT up-regulation in MI was accompanied by deregulation of some fibrosis-related regulators: down-regulation of miR-24 and up-regulation of Furin and TGF-β1. Most notably, knockdown of endogenous MIAT by its siRNA reduced cardiac fibrosis and improved cardiac function and restored the deregulated expression of the fibrosis-related regulators. In cardiac fibroblasts treated with serum or angiotensin II, similar up-regulation of MIAT and down-regulation of miR-24 were consistently observed. These changes promoted fibroblasts proliferation and collagen accumulation, whereas knockdown of MIAT by siRNA or overexpression of miR-24 with its mimic abrogated the fibrogenesis. Our study therefore has identified MIAT as the first pro-fibrotic lncRNA in heart and unraveled the role of MIAT in the pathogenesis of MI. These findings also promise that normalization of MIAT level may prove to be a therapeutic option for the treatment of MI-induced cardiac fibrosis and the associated cardiac dysfunction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|