EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay.
EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay.
复制标题
DOI：
10.1371/journal.pone.0091849
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Vavvas DG
中科院分区：
文献类型：
--
作者：
Takeuchi K;Yanai R;Kumase F;Morizane Y;Suzuki J;Kayama M;Brodowska K;Nakazawa M;Miller JW;Connor KM;Vavvas DG
Egfl7是一种分泌型血管生成因子，与已知的分泌型血管生成分子血管内皮生长因子和成纤维细胞生长因子-2不同，它几乎只由内皮细胞表达，并可能以自分泌的方式发挥作用。先前的研究表明，EGFL7通过干扰Notch通路和/或通过内含子miR126来介导其血管生成效应。关于它对血管内皮生长因子信号转导的影响，人们知之甚少。我们希望通过体外Matrigel包埋小鼠眼杯实验和siRNA介导的siRNA下调EGFL7来研究表皮生长因子样结构域7(EGFL7)在血管生成中的作用。我们的结果表明，在siRNA下调EGFL7后，VEGF诱导的血管形成明显受损。此外，EGFL7基因敲除可抑制血管内皮细胞中磷酸化Akt和磷酸化Erk(1/2)的表达，但不改变VEGFR的磷酸化和Neu Pilin-1蛋白的表达或miR126的表达。综上所述，EGFL7是血管生成过程中上调Akt/Erk(1/2)通路所必需的，可能是病理性新生血管疾病的一个新的治疗靶点。
EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization.
登录
查看更多内容
DOI：
10.1186/2040-2384-2-9
发表时间：
2010-06-08
期刊：
Journal of angiogenesis research
影响因子：
--
作者：
Nikolic I;Plate KH;Schmidt MHH
通讯作者：
Schmidt MHH
影响因子：
2.5
作者：
Fitch, MJ;Campagnolo, L;Stuhlmann, H
通讯作者：
Stuhlmann, H
影响因子：
64.8
作者：
Parker, LH;Schmidt, M;Ye, WL
通讯作者：
Ye, WL
影响因子：
64.8
作者：
Risau, W
通讯作者：
Risau, W
影响因子：
4.2
作者：
ADAMIS, AP;MILLER, JW;YEO, KT
通讯作者：
YEO, KT