A novel reciprocal loop between microRNA-21 and TGFβRIII is involved in cardiac fibrosis
A novel reciprocal loop between microRNA-21 and TGFβRIII is involved in cardiac fibrosis
复制标题
microRNA-21 和TGFβRIII 之间的一种新的相互循环参与心脏纤维化。
DOI：
10.1016/j.biocel.2012.08.019
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发表时间：
2012-12-01
影响因子：
4
通讯作者：
Yang, Baofeng
中科院分区：
文献类型：
--
作者：
Liang, Haihai;Zhang, Chun;Yang, Baofeng
Cardiac fibrosis is characterized by aberrant proliferation of cardiac fibroblasts and exaggerated deposition of extracellular matrix (ECM) in the myocardial interstitial, and ultimately impairs cardiac function. It is still controversial whether microRNA-21 (miR-21) participates in the process of cardiac fibrosis. Our previous study confirmed that transforming growth factor beta receptor III (TGF beta RIII) is a negative regulator of TGF-beta pathway. Here, we aimed to decipher the relationship between miR-21 and TGF beta RIII in the pathogenic process of myocardial fibrosis. We found that TGF-beta 1 and miR-21 were up-regulated, whereas TGF beta RIII was down-regulated in the border zone of mouse hearts in response to myocardial infarction. After transfection of miR-21 into cardiac fibroblasts, TGF beta RIII expression was markedly reduced and collagen content was increased. And, luciferase results confirmed that TGF beta RIII was a target of miR-21. It suggests that up-regulation of miR-21 could increase the collagen content and at least in part through inhibiting TGF beta RIII. Conversely, we also confirmed that overexpression of TGF beta RIII could inhibit the expression of miR-21 and reduce collagen production in fibroblasts. Further studies showed that overexpression of TGF beta RIII could also deactivate TGF-beta 1 pathway by decreasing the expression of TGF-beta 1 and phosphorylated-Smad3 (p-Smad3). TGF-beta 1 has been proven as a positive regulator of miR-21. Taken together, we found a novel reciprocal loop between miR-21 and TGF beta RIII in cardiac fibrosis caused by myocardial infarction in mice, and targeting this pathway could be a new strategy for the prevention and treatment of myocardial remodeling. Crown Copyright (c) 2012 Published by Elsevier Ltd. All rights reserved.
