The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling.
The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling.
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DOI：
10.1016/j.devcel.2014.11.016
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发表时间：
2015-01-12
影响因子：
11.8
通讯作者：
Randi, Anna M.
中科院分区：
文献类型：
--
作者：
Birdsey, Graeme M.;Shah, Aarti V.;Dufton, Neil;Reynolds, Louise E.;Almagro, Lourdes Osuna;Yang, Youwen;Aspalter, Irene M.;Khan, Samia T.;Mason, Justin C.;Dejana, Elisabetta;Goettgens, Berthold;Hodivala-Dilke, Kairbaan;Gerhardt, Holger;Adams, Ralf H.;Randi, Anna M.
血管稳定性对于胚胎发育至关重要；在成人中，许多疾病都与血管完整性的丧失有关。 ETS 转录因子 ERG 驱动 VE-钙粘蛋白的表达并控制连接完整性。我们发现，小鼠 ERG 的组成性内皮缺失 (ErgcEC-KO) 会导致胚胎死亡并伴有血管缺陷。 ERG 的诱导性内皮缺失（ErgiEC-KO）会导致出生后视网膜和肿瘤中的生理和病理性血管生成缺陷，并降低血管稳定性。 ERG 通过 VE-钙粘蛋白和 Wnt 受体 Frizzled-4 介导的信号促进 β-连环蛋白稳定性，从而控制 Wnt/β-连环蛋白通路。 ERG 缺陷的内皮细胞中 Wnt 信号传导减少；用氯化锂激活 Wnt 信号，稳定 β-连环蛋白水平，纠正 ErgcEC-KO 胚胎中的血管缺陷。最后，ERG 在体内的过度表达会降低 VEGF 诱导的血管的通透性并增加稳定性。这些数据表明 ERG 通过 Wnt 信号传导是血管生成和血管稳定性的重要调节剂。小鼠内皮 ERG 的诱导缺失会导致血管生成缺陷 ERG 通过 Wnt/β-连环蛋白信号控制血管稳定性 β-连环蛋白激活可挽救 ERG 缺陷小鼠体内的血管生成缺陷 体内 ERG 的过度表达可稳定 VEGF 诱导的血管生成 Birdsey，Shah 等人。表明内皮 ETS 因子 ERG 通过 VE-钙粘蛋白和 Wnt 受体 Frizzled-4 介导的途径促进 β-连环蛋白稳定性来控制 Wnt/β-连环蛋白信号传导。在体内，ERG 过度表达可稳定 VEGF 依赖性血管生成。因此，ERG 是通过 Wnt 信号传导调节血管生成和血管稳定性的重要调节剂。
Blood vessel stability is essential for embryonic development; in the adult, many diseases are associated with loss of vascular integrity. The ETS transcription factor ERG drives expression of VE-cadherin and controls junctional integrity. We show that constitutive endothelial deletion of ERG (ErgcEC-KO) in mice causes embryonic lethality with vascular defects. Inducible endothelial deletion of ERG (ErgiEC-KO) results in defective physiological and pathological angiogenesis in the postnatal retina and tumors, with decreased vascular stability. ERG controls the Wnt/β-catenin pathway by promoting β-catenin stability, through signals mediated by VE-cadherin and the Wnt receptor Frizzled-4. Wnt signaling is decreased in ERG-deficient endothelial cells; activation of Wnt signaling with lithium chloride, which stabilizes β-catenin levels, corrects vascular defects in ErgcEC-KO embryos. Finally, overexpression of ERG in vivo reduces permeability and increases stability of VEGF-induced blood vessels. These data demonstrate that ERG is an essential regulator of angiogenesis and vascular stability through Wnt signaling. Inducible deletion of endothelial ERG in mice causes defective angiogenesis ERG controls vascular stability through Wnt/β-catenin signaling β-catenin activation rescues the angiogenic defect in vivo in ERG-deficient mice Overexpression of ERG in vivo stabilizes VEGF-induced angiogenesis Birdsey, Shah et al. show that the endothelial ETS factor ERG controls Wnt/β-catenin signaling by promoting β-catenin stability, through pathways mediated by VE-cadherin and the Wnt receptor Frizzled-4. In vivo, ERG overexpression stabilizes VEGF-dependent angiogenesis. Thus, ERG is an essential regulator of angiogenesis and vascular stability through Wnt signaling.
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DOI：
10.1158/1940-6207.capr-11-0077
发表时间：
2011-09
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Li Y;Kong D;Wang Z;Ahmad A;Bao B;Padhye S;Sarkar FH
通讯作者：
Sarkar FH
影响因子：
11.8
作者：
Corada M;Nyqvist D;Orsenigo F;Caprini A;Giampietro C;Taketo MM;Iruela-Arispe ML;Adams RH;Dejana E
通讯作者：
Dejana E
影响因子：
4.6
作者：
Korn, Claudia;Scholz, Beate;Augustin, Iris
通讯作者：
Augustin, Iris
影响因子：
30.5
作者：
Loughran, Stephen J.;Kruse, Elizabeth A.;Kile, Benjamin T.
通讯作者：
Kile, Benjamin T.
影响因子：
20.3
作者：
Giampietro, Costanza;Taddei, Andrea;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta