权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Identification of endothelial cell-specific signal transaction pathways leading to angiogenic cellular responses

鉴定导致血管生成细胞反应的内皮细胞特异性信号处理途径

基本信息

批准号：
13470337
负责人：
KANDA Shigeru
金额：
$ 6.27万
依托单位：
Nagasaki University Graduate School of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470337/
关键词：
angiogenesis endothelial cells c-Fes c-Fyn FGF-2 tube formation stromal cell-derived factor-1 sonic hedgehog FGF Tie2 シグナル伝達

项目摘要

We investigated the signal transduction pathways leading to cellular responses of endothelial cells for establishment of endothelial cell-specific antiangiogenic therapy. C-Fes is a protein tyrosine kinase, which is exclusively expressed in endothelial cells as well as hematopoietic cells. We identified that angiopoietin 2 (Ang2) induced migration and tube formation by nurine brain capillary endothelial cells, denoted IBE cells. Ang2-induced migration was dependent on phosphoinositide 3-kinase (PI3-kinase) and activation of PI3-kinase required c-Fes activity. In cells treated with stromal cell-derived factor-1 (SDF-1) and sonic hedgehog (Shh) also induced tube formation of endothelial cells in PI3-kinase- and c-Fes-dependent manner. These results indicate that c-Fes and is important for ligand-dependent activation of PI3-kinase and subsequent cellular responses of endothelial cells. Tube formation was regulated by c-Fyn, a member of Src family protein tyrosine kinase, in FGF-2- and Ang2-treated cells, suggesting that c-Fyn plays pivotal role in tube formation of endothelial cells. To examine the details of downstream signaling pathways of c-Fes and c-Fyn would thus be great importance to find new targets for antiangiogenic therapies, which are specific for endothelial cells.

我们研究了导致内皮细胞细胞反应的信号转导途径，以建立内皮细胞特异性的抗血管生成治疗。C-Fes是一种蛋白酪氨酸激酶，在血管内皮细胞和造血细胞中均有表达。我们发现血管生成素2(Ang2)可诱导牛脑毛细血管内皮细胞(IBE细胞)迁移和形成管状结构。ANG2诱导的迁移依赖于磷脂酰肌醇3-激酶(PI3-K)，而PI3-K的激活需要c-Fes活性。在基质细胞衍生因子-1(SDF-1)和Sonic Hedgehog(Shh)处理的细胞中，也以PI3-激酶和c-Fes依赖的方式诱导内皮细胞形成管状结构。这些结果表明，c-Fes和在配体依赖的PI3-激酶激活和随后的内皮细胞反应中是重要的。在经血管内皮细胞生长因子-2和血管紧张素Ⅱ处理的细胞中，c-Fyn蛋白酪氨酸激酶家族成员c-Fyn对血管内皮细胞管状结构的形成起着重要的调节作用。因此，研究c-Fes和c-Fyn下游信号通路的细节对于寻找针对内皮细胞的抗血管生成治疗的新靶点具有重要意义。