MiR-155 Knockout in Fibroblasts Improves Cardiac Remodeling by Targeting Tumor Protein p53-Inducible Nuclear Protein 1
MiR-155 Knockout in Fibroblasts Improves Cardiac Remodeling by Targeting Tumor Protein p53-Inducible Nuclear Protein 1
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DOI：
10.1177/1074248415616188
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发表时间：
2016-07-01
影响因子：
2.6
通讯作者：
Xiao, Yali
中科院分区：
文献类型：
--
作者：
He, Wangwei;Huang, He;Xiao, Yali
急性心肌梗死(AMI)引起的心脏重构是心力衰竭研究的一大挑战。MIR-155已被确定为心脏炎症和肥大的关键介质。在本研究中，我们探讨了miR-155在急性心肌梗死所致心脏重构中的作用。我们证明在心脏成纤维细胞中表达的miR-155是心脏重塑的一个重要因素。我们发现，在体内，miR-155基因敲除改善了左心功能，缩小了梗死面积，减少了胶原沉积，而miR-155的过度表达产生了相反的作用。MiR-155基因敲除也抑制心脏成纤维细胞的增殖和向肌成纤维细胞的分化。此外，小干扰RNA下调肿瘤蛋白P53诱导的核蛋白1(TP53INP1)可逆转miR-155基因敲除对心脏成纤维细胞的影响。我们的数据显示，敲除心脏成纤维细胞中的miR-155可以通过靶向TP53INP1来改善心脏重构，这可能是一种新的心脏重构治疗策略。
Cardiac remodeling caused by acute myocardial infarction (AMI) represents a major challenge for heart failure research. MiR-155 has been identified as a key mediator of cardiac inflammation and hypertrophy. In this study, we investigate the role of miR-155 in cardiac remodeling induced by AMI. We demonstrate that miR-155 expressed in cardiac fibroblasts is a potent contributor to cardiac remodeling. We reveal that in vivo, miR-155 knockout improves left ventricular function, reduces infarct size, and attenuates collagen deposition, whereas overexpression of miR-155 produces the opposite effects. MiR-155 knockout also inhibits cardiac fibroblast proliferation and differentiation into myofibroblasts. In addition, downregulation of tumor protein p53-inducible nuclear protein 1 (TP53INP1) by small interfering RNA reverses the effects of miR-155 knockout on cardiac fibroblasts. Our data reveal that knockout of miR-155 in cardiac fibroblasts improves cardiac remodeling by targeting TP53INP1, which may be a novel treatment strategy for cardiac remodeling.