Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 35, Issue 1, Pages 213-226Publisher
KARGER
DOI: 10.1159/000369689
Keywords
Cardiac fibroblasts; Hypoxia; MicroRNAs; Transforming growth factor beta receptor I; Cardiac fibrosis
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Funding
- Natural Science Foundation of China [30971242]
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Background/Aims: Hypoxia is a basic pathological challenge that is associated with numerous cardiovascular disorders including aberrant cardiac remodeling. Transforming growth factor beta (TGF-beta) signaling pathway plays a pivotal role in mediating cardiac fibroblast (CF) function and cardiac fibrosis. Recent data suggested that microRNA-101a (miR-101a) exerted anti-fibrotic effects in post-infarct cardiac remodeling and improved cardiac function. This study aimed to investigate the potential relationship between hypoxia, miR-101a and TGF-beta signaling pathway in CFs. Methods and Results: Two weeks following coronary artery occlusion in rats, the expression levels of both TGF beta 1 and TGF beta RI were increased, but the expression of miR-101a was decreased at the site of the infarct and along its border. Cultured rat neonatal CFs treated with hypoxia were characterized by the up-regulation of TGF beta 1 and TGF beta RI and the down-regulation of miR-101a. Delivery of miR-101a mimics significantly suppressed the expression of TGF beta RI and p-Smad 3, CF differentiation and collagen content of CFs. These anti-fibrotic effects were abrogated by co-transfection with AMO-miR-101a, an antisense inhibitor of miR-101a. The repression of TGF beta RI, a target of miR-101a, was validated by luciferase reporter assays targeting the 3'UTR of TGF beta RI. Additionally, we found that overexpression of miR-101a reversed the improved migration ability of CFs and further reduced CF proliferation caused by hypoxia. Conclusion: Our study illustrates that miR-101a exerts anti-fibrotic effects by targeting TGF beta RI, suggesting that miR-101a plays a multi-faceted role in modulating TGF-beta signaling pathway and cardiac fibrosis. Copyright (C) 2015 S. Karger AG, Basel
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