J Cell Mol Med：microRNA-24调节心肌梗死后心肌纤维化

shiliangyin

J Cell Mol Med：microRNA-24调节心肌梗死后心肌纤维化
心肌梗死（MI)后心肌纤维化已被确定为是心脏衰竭发展的关键因素。虽然参与心脏各种病理生理过程中失调的miRNA众所周知，但miRNA在调节心肌梗死后纤维化中的作用尚不清楚。
早期研究观察到纤维化和心肌肥厚的miR-24表达之间的关系，近日，研究人员在J Cell Mol Med杂志上发表研究评估miR-24是如何调节心肌梗死后纤维化的。使用qRT-PCR发现microRNA-24在心肌梗死的心脏中是下调的，下调的miR-24表达与细胞外基质（ECM）重塑密切相关。
在体内，在MI后2个星期内通过慢病毒注射miR-24到心脏梗死边缘区能改善心脏功能和衰减纤维化。此外，在体外实验表明通过合成miR-24前体上调miR-24可以减少纤维化和降低心脏成纤维细胞（CFS）的分化和迁移。
TGF-β能增加miR-24的表达，过表达的miR-24会减少心脏成纤维细胞中TGF-β的分泌以及Smad2/3的磷酸化。利用微阵列分析和生物信息学分析发现，弗林蛋白酶是一个miR-24在肝纤维化中的潜在作用靶蛋白。
最后，研究表明心脏成纤维细胞中的miR-24调节弗林蛋白酶的蛋白和mRNA水平。这些结果表明，miR-24通过调控弗林蛋白酶-TGF-β信号途径在心脏成纤维细胞功能和心肌梗死后心肌纤维化中发挥重要作用。因此，miR-24可作为用于治疗心肌梗塞和其他纤维化心脏疾病的靶标。（生物谷：Bioon.com）



doi:10.1111/j.1582-4934.2012.01523.x
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MicroRNA-24 Regulates Cardiac Fibrosis after Myocardial Infarction

Jue Wang1,2,3,4, Weicong Huang1,4, Ruixia Xu1,2,3, Yu Nie1,2,3, Xiaoqing Cao1,2,3, Jiang Meng1,2,3, Xiuqing Xu1,2,3, Shengshou Hu1,2,3, Zhe Zheng1,2,3,*
Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure. Although dysregulation of miRNAs is involved in various pathophysiologic processes in the heart, the role of miRNA in fibrosis regulation after MI is unclear. Previously we observed the correlation between fibrosis and the miR-24 expression in hypertrophic hearts, here we assessed how miR-24 regulates fibrosis after MI. Using qRT-PCR, we showed that microRNA-24 was down-regulated in the MI heart, the change in miR-24 expression was closely related to extracellular matrix (ECM) remodeling. In vivo, miR-24 could improve heart function and attenuate fibrosis in the infarct border zone of the heart 2 weeks after MI through intramyocardial injection of Lentiviruses. Moreover, in-vitro experiments suggested that up-regulation of miR-24 by synthetic miR-24 precursors could reduce fibrosis and also decrease the differentiation and migration of cardiac fibroblasts(CFs). TGF-β (a pathologic mediator of fibrotic disease) increased miR-24 expression, over-expression of miR-24 reduced TGF-β secretion and Smad2/3 phosphorylation in cardiac fibroblasts. Using microarray analyses and bioinformatics analyses, we found furin to be a potential target for miR-24 in fibrosis (furin is a protease which control latent TGF-β activation processing). Finally, we demonstrated that protein and mRNA levels of furin were regulated by miR-24 in cardiac fibroblasts. These findings suggest that miR-24 has a critical role in cardiac fibroblast function and cardiac fibrosis after MI through a furin–TGF-β pathway. Thus, miR-24 may be used as a target for treatment of MI and other fibrotic heart diseases.

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