miR-126 regulates angiogenic signaling and vascular integrity.
miR-126 regulates angiogenic signaling and vascular integrity.
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DOI：
10.1016/j.devcel.2008.07.008
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发表时间：
2008-08
影响因子：
11.8
通讯作者：
Srivastava, Deepak
中科院分区：
文献类型：
--
作者：
Fish, Jason E.;Santoro, Massimo M.;Morton, Sarah U.;Yu, Sangho;Yeh, Ru-Fang;Wythe, Joshua D.;Lvey, Kathryn N.;Bruneau, Benoit G.;Stainier, Didier Y. R.;Srivastava, Deepak
血管系统的形成、维持和重塑的精确调节是正常发育、组织对损伤的反应和肿瘤进展所必需的。特定的microRNA如何与血管生成信号级联交叉并调节血管生成信号级联尚不清楚。在这里，我们鉴定了在源自小鼠胚胎干（ES）细胞的内皮细胞和发育中的小鼠胚胎中富集的microRNA。我们发现miR-126调节内皮细胞对VEGF的反应。此外，斑马鱼中miR-126的敲低导致胚胎发育期间血管完整性丧失和出血。miR-126部分通过直接抑制VEGF途径的负调节因子发挥作用，包括Sprouty相关蛋白SPRED 1和磷酸肌醇-3激酶调节亚基2（PIK 3R 2）。斑马鱼中Spred 1表达增加或VEGF信号抑制导致类似于miR-126敲低的缺陷。这些发现说明单个miRNA可以调节血管完整性和血管生成，为调节血管形成和功能提供了新的靶点。
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, and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2). 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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影响因子：
20.1
作者：
Kuehbacher, Angelika;Urbich, Carmen;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
64.5
作者：
Lu, Q;Sun, EE;Flanagan, JG
通讯作者：
Flanagan, JG
影响因子：
4.8
作者：
Kim, I;Ryu, YS;Koh, GY
通讯作者：
Koh, GY
影响因子：
20.3
作者：
Chen, Yun;Gorski, David H.
通讯作者：
Gorski, David H.
DOI：
10.1073/pnas.0706901104
发表时间：
2007-12-18
影响因子：
11.1
作者：
Lee, Daniel Y.;Deng, Zhaoqun;Yang, Burton B.
通讯作者：
Yang, Burton B.