精确调控血管的生成,维护和重塑是机体发展,组织伤害应急和肿瘤形成所必需的.然而,我们还不知道MicroRNA是如何与调节血管生成的信号级联相关.在这篇文章中,我们验证了在小鼠胚胎干细胞里分离出来的内皮细胞和发育中的小鼠胚胎中MicroRNA的含量十分丰富.我们还找出:在内皮细胞中,miR-126调控细胞对内皮生长因子(VEGF)的效应机制.另外,把斑马鱼中的miR-126敲除以后会导致胚胎发育过程中血管形成不完整与造血功能缺失.miR-126的其中一部分功能就是抑制VEGF信号通路的阻抑调控,其中包括Sprouty相关蛋白SPRED1和磷酸肌醇激酶3的II型调节亚基(PIK3R2/p85-b).增加斑马鱼里SPRED1或者VEGF信号通路相关抑制因子的表达,可以得到与敲除miR-126实验一样的结果.这些能说明单链小分子RNA可以调控血管生成及其完整性,为研究血管的形成及其功能指出了一个新的方向.

miR-126 Regulates Angiogenic Signaling and Vascular Integrity

SUMMARY:
    Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 andphosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-b). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.

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