MicroRNA-328, a Potential Anti-Fibrotic Target in Cardiac Interstitial Fibrosis

Background/Aims: Deregulated myocardial fibrosis is associated with a wide spectrum of cardiac conditions, being considered one of the major causes for heart disease. Our study was designed to investigate the role of microRNA-328 (miR-328) in regulating cardiac fibrosis. Methods: We induced cardiac...

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Main Authors: Weijie Du, Haihai Liang, Xu Gao, Xiaoxue Li, Yue Zhang, Zhenwei Pan, Cui Li, Yuying Wang, Yanxin Liu, Wei Yuan, Ning Ma, Wenfeng Chu, Hongli Shan, Yanjie Lu
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2016-08-01
Series:Cellular Physiology and Biochemistry
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Online Access:http://prod.karger.com/Article/FullText/447793
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Summary:Background/Aims: Deregulated myocardial fibrosis is associated with a wide spectrum of cardiac conditions, being considered one of the major causes for heart disease. Our study was designed to investigate the role of microRNA-328 (miR-328) in regulating cardiac fibrosis. Methods: We induced cardiac fibrosis following MI by occlusion of the left coronary artery in C57BL/6 mice. Real-time PCR was employed to evaluate the level of miR-328. Masson's Trichrome stain was used to evaluate the development of fibrosis. Luciferase activity assay was performed to confirm the miRNA's binding site in the TGFβRIII gene. Western blot analysis was used to examine TGFβRIII, p-smad2/3 and TGF-β1 at protein level. Results: In this study, we found that miR-328 was significantly upregulated in the border zone of infarcted myocardium of wild type (WT) mice; TGFβRIII was downregulated whereas TGF-β1 was upregulated along with increased cardiac fibrosis. And miR-328 stimulated TGF-β1 signaling and promoted collagen production in cultured fibroblasts. We further found that the pro-fibrotic effect of miR-328 was mediated by targeting TGFβRIII. Additionally, cardiac fibrosis was significantly reduced in infarcted heart when treated with miR-328 antisense. Conclusions: These data suggest that miR-328 is a potent pro-fibrotic miRNA and an important determinant of cardiac fibrosis in diseased heart.
ISSN:1015-8987
1421-9778