The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis.
The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis.
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DOI：
10.1016/j.devcel.2008.07.002
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发表时间：
2008-08
影响因子：
11.8
通讯作者：
Olson, Eric N.
中科院分区：
文献类型：
--
作者：
Wang, Shusheng;Aurora, Arin B.;Johnson, Brett A.;Qi, Xiaoxia;McAnally, John;Hill, Joseph A.;Richardson, James A.;Bassel-Duby, Rhonda;Olson, Eric N.
内皮细胞在维持血管完整性、血管生成和创伤修复中起重要作用。我们发现，内皮细胞限制性microRNA（miR-126）介导体内发育血管生成。在小鼠中靶向缺失miR-126会导致血管渗漏、老化和部分胚胎死亡，这是由于血管完整性的丧失以及内皮细胞增殖、迁移和血管生成的缺陷。存活的突变动物亚组显示心肌梗死后心脏新生血管形成缺陷。miR-126突变小鼠的血管异常类似于血管生成生长因子（如VEGF和FGF）信号转导减弱的结果。因此，miR-126增强VEGF和FGF的促血管生成作用，并通过抑制血管生成信号的细胞内抑制剂Spred-1的表达来促进血管形成。这些发现对涉及异常血管生成和血管渗漏的各种疾病具有重要的治疗意义。
Endothelial cells play essential roles in maintenance of vascular integrity, angiogenesis and wound repair. We show that an endothelial cell-restricted microRNA (miR-126) mediates developmental angiogenesis in vivo. Targeted deletion of miR-126 in mice causes leaky vessels, hemorrhaging, and partial embryonic lethality, due to a loss of vascular integrity and defects in endothelial cell proliferation, migration and angiogenesis. The subset of mutant animals that survives displays defective cardiac neovascularization following myocardial infarction. The vascular abnormalities of miR-126 mutant mice resemble the consequences of diminished signaling by angiogenic growth factors, such as VEGF and FGF. Accordingly, miR-126 enhances the pro-angiogenic actions of VEGF and FGF and promotes blood vessel formation by repressing the expression of Spred-1, an intracellular inhibitor of angiogenic signaling. These findings have important therapeutic implications for a variety of disorders involving abnormal angiogenesis and vascular leakage.
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