The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis
The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis
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DOI：
10.1182/blood-2012-04-423004
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发表时间：
2012-12-13
期刊：
影响因子：
20.3
通讯作者：
Boshoff, Chris
中科院分区：
文献类型：
--
作者：
Bridge, Gemma;Monteiro, Rui;Boshoff, Chris
Delta-like 4（DLL 4）是Notch信号家族的一种膜结合配体，在血管发育和血管生成中起着重要作用。我们鉴定了一个保守的microRNA家族，miR-30，其靶向DLL 4。内皮细胞中miR-30 b的过表达导致出芽血管生成的体外模型中血管数量和长度增加。将miR-30模拟物显微注射到斑马鱼胚胎中导致dll 4的抑制和随后的节段间血管的过度出芽以及背主动脉直径的减小。使用针对dll 4 3 'UTR内的miR-30位点的靶保护剂上调dll 4并与Vegfa信号转导敲低协同抑制血管生成。此外，在卡波西肉瘤疱疹病毒（KSHV）感染期间恢复miR-30 b或miR-30 c表达减弱了DLL 4的病毒诱导。总之，这些结果表明miR-30家族对DLL 4的高度保守的分子靶向调节血管生成。（血。2012; 120（25）：5063-5072）
Delta-like 4 (DLL4), a membrane-bound ligand belonging to the Notch signaling family, plays a fundamental role in vascular development and angiogenesis. We identified a conserved microRNA family, miR-30, which targets DLL4. Overexpression of miR-30b in endothelial cells led to increased vessel number and length in an in vitro model of sprouting angiogenesis. Microinjection of miR-30 mimics into zebrafish embryos resulted in suppression of dll4 and subsequent excessive sprouting of intersegmental vessels and reduction in dorsal aorta diameter. Use of a target protector against the miR-30 site within the dll4 3'UTR up-regulated dll4 and synergized with Vegfa signaling knockdown to inhibit angiogenesis. Furthermore, restoration of miR-30b or miR-30c expression during Kaposi sarcoma herpesvirus (KSHV) infection attenuated viral induction of DLL4. Together these results demonstrate that the highly conserved molecular targeting of DLL4 by the miR-30 family regulates angiogenesis. (Blood. 2012; 120(25): 5063-5072)