MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice
MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice
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DOI：
10.1126/science.1174381
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发表时间：
2009-06-26
期刊：
影响因子：
56.9
通讯作者：
Dimmeler, Stefanie
中科院分区：
文献类型：
--
作者：
Bonauer, Angelika;Carmona, Guillaume;Dimmeler, Stefanie
MicroRNAs(MiRs)是一种小的非编码RNA，通过与靶信使RNA(MRNAs)结合来调节基因的表达，导致翻译抑制或降解。在这里，我们证明了类似于92簇的miR-17在人内皮细胞中高度表达，并且该簇的一个成分miR-92a控制着新血管的生长(血管生成)。在体内和体外，强制过表达miR-92a内皮细胞可阻断血管生成。在肢体缺血和心肌梗死的小鼠模型中，全身应用一种旨在抑制miR-92a的Anagomir可以促进血管生长和受损组织的功能恢复。MIR-92a似乎针对几个促血管生成蛋白的mRNAs，包括整合素亚单位α5。因此，miR-92a可能成为治疗缺血性疾病的有价值的靶点。
MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Here, we show that the miR-17 similar to 92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis). Forced overexpression of miR-92a in endothelial cells blocked angiogenesis in vitro and in vivo. In mouse models of limb ischemia and myocardial infarction, systemic administration of an antagomir designed to inhibit miR-92a led to enhanced blood vessel growth and functional recovery of damaged tissue. MiR-92a appears to target mRNAs corresponding to several proangiogenic proteins, including the integrin subunit alpha5. Thus, miR-92a may serve as a valuable therapeutic target in the setting of ischemic disease.