血管生成
生物
新生血管
小RNA
细胞生物学
成纤维细胞生长因子
内皮干细胞
血管内皮生长因子
癌症研究
血管内皮生长因子A
萌芽血管生成
脐静脉
遗传学
血管内皮生长因子受体
体外
基因
受体
作者
Shusheng Wang,Arin B. Aurora,Brett A. Johnson,Xiaoxia Qi,John McAnally,Joseph A. Hill,James A. Richardson,Rhonda Bassel‐Duby,Eric N. Olson
标识
DOI:10.1016/j.devcel.2008.07.002
摘要
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 proangiogenic 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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