MicroRNA-24 regulates cardiac fibrosis after myocardial infarction.
MicroRNA-24 regulates cardiac fibrosis after myocardial infarction.
复制标题
DOI：
10.1111/j.1582-4934.2012.01523.x
复制
发表时间：
2012-09
影响因子：
5.3
通讯作者：
Zheng Z
中科院分区：
文献类型：
--
作者：
Wang J;Huang W;Xu R;Nie Y;Cao X;Meng J;Xu X;Hu S;Zheng Z
心肌梗塞（MI）后的心脏纤维化已被确定为心力衰竭发展的关键因素。尽管microRNA (miRNA)的失调参与心脏的多种病理生理过程，但miRNA在MI后纤维化调节中的作用尚不清楚。之前我们观察了肥厚心脏中纤维化与 miR-24 表达之间的相关性，本文中我们评估了 miR-24 如何调节 MI 后的纤维化。使用 qRT-PCR，我们发现 miR-24 在 MI 心脏中下调； miR-24表达的变化与细胞外基质（ECM）重塑密切相关。在体内，通过心肌内注射慢病毒，miR-24可以在MI后两周改善心脏功能并减轻心脏梗塞边缘区的纤维化。此外，体外实验表明，合成的 miR-24 前体上调 miR-24 可以减少纤维化，还可以减少心脏成纤维细胞 (CF) 的分化和迁移。 TGF-β（纤维化疾病的病理介质）增加 miR-24 表达，miR-24 过度表达减少 CF 中 TGF-β 分泌和 Smad2/3 磷酸化。通过进行微阵列分析和生物信息学分析，我们发现弗林蛋白酶是纤维化中 miR-24 的潜在靶标（弗林蛋白酶是一种控制潜在 TGF-β 激活过程的蛋白酶）。最后，我们证明了 CF 中弗林蛋白酶的蛋白和 mRNA 水平受到 miR-24 的调节。这些发现表明，miR-24 通过弗林蛋白酶-TGF-β 途径在心肌梗死后的 CF 功能和心脏纤维化中发挥关键作用。因此，miR-24可用作治疗MI和其他纤维化心脏病的靶标。
Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure. Although dysregulation of microRNA (miRNA) is involved in various pathophysiological processes in the heart, the role of miRNA in fibrosis regulation after MI is not clear. Previously we observed the correlation between fibrosis and the miR-24 expression in hypertrophic hearts, herein we assessed how miR-24 regulates fibrosis after MI. Using qRT-PCR, we showed that miR-24 was down-regulated in the MI heart; the change in miR-24 expression was closely related to extracellular matrix (ECM) remodelling. In vivo, miR-24 could improve heart function and attenuate fibrosis in the infarct border zone of the heart two 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 pathological mediator of fibrotic disease) increased miR-24 expression, overexpression of miR-24 reduced TGF-β secretion and Smad2/3 phosphorylation in CFs. By performing microarray analyses and bioinformatics analyses, we found furin to be a potential target for miR-24 in fibrosis (furin is a protease which controls latent TGF-β activation processing). Finally, we demonstrated that protein and mRNA levels of furin were regulated by miR-24 in CFs. These findings suggest that miR-24 has a critical role in CF 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.
登录
查看更多内容
影响因子：
5.6
作者：
Luna, Coralia;Li, Guorong;Qiu, Jianming;Epstein, David L.;Gonzalez, Pedro
通讯作者：
Gonzalez, Pedro
影响因子：
37.8
作者：
Hu S;Huang M;Li Z;Jia F;Ghosh Z;Lijkwan MA;Fasanaro P;Sun N;Wang X;Martelli F;Robbins RC;Wu JC
通讯作者：
Wu JC
影响因子：
5.3
作者：
Manole CG;Cismaşiu V;Gherghiceanu M;Popescu LM
通讯作者：
Popescu LM
影响因子：
15.9
作者：
Ornatowski, Wojciech;Poschet, Jens F.;Deretic, Vojo
通讯作者：
Deretic, Vojo
影响因子：
48
作者：
Gentner, Bernhard;Schira, Giulia;Naldini, Luigi
通讯作者：
Naldini, Luigi