Neuropilin-1 on hematopoietic cells as a source of vascular development.
Neuropilin-1 on hematopoietic cells as a source of vascular development.
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Neuropilin-1 对造血细胞的作用作为血管发育的来源。
DOI：
10.1182/blood-2002-01-0119
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发表时间：
2003
期刊：
影响因子：
20.3
通讯作者：
N. Takakura
中科院分区：
文献类型：
--
作者：
Yoshihiro Yamada;Y. Oike;H. Ogawa;Yasuhiro Ito;H. Fujisawa;T. Suda;N. Takakura
神经匹林-1(NP-1)是血管内皮生长因子-165(VEGF165)的受体，它作为辅助受体通过血管内皮生长因子受体-2(VEGFR-2)增强VEGF165的功能。使用NP-1转基因和敲除小鼠的研究表明，这种分子对血管发育和神经元发育都很重要。我们最近报道，聚集型可溶性NP-1通过低剂量的VEGF165磷酸化血管内皮细胞上的VEGFR-2，在体外和体内挽救了NP-1/-胚胎的血管缺陷。在这里，我们证明了NP-1是由胎肝中CD45+的造血细胞表达的，可以结合VEGF165，并使血管内皮细胞上的VEGFR-2磷酸化。CD45+NP-1+细胞挽救了在NP-1-/-P-Sp(腹主动脉旁内脏胸膜中胚层区)培养中缺陷的血管生成和血管生成，而CD45+NP-1-细胞不能。此外，在体内Matrigel实验和角膜新生血管实验中，CD45+NP-1+细胞和VEGF165共同诱导血管生成。NP-1的胞外区由a、b和c区组成，已知a区和c区是NP-1二聚化所必需的。我们发现，在NP-1突变体中，“a”和“c”结构域对于挽救有缺陷的血管是必不可少的。这些结果表明，NP-1以外源性的方式促进血管生成和血管生成，NP-1的二聚化对促进血管发育具有重要意义。在NP-1-/-胚胎中，血管发芽在中枢神经系统(CNS)和心包组织中受到损害，那里的血管生长因子含量不高，这表明表达NP-1的细胞是正常血管发育所必需的。
Neuropilin-1 (NP-1) is a receptor for vascular endothelial growth factor-165 (VEGF165) and acts as a coreceptor that enhances the function of VEGF165 through VEGF receptor-2 (VEGFR-2). Studies using transgenic and knock-out mice of NP-1 indicated that this molecule is important for vascular development as well as neuronal development. We recently reported that clustered soluble NP-1 phosphorylates VEGFR-2 on endothelial cells with a low dose of VEGF165 and rescues the defective vascularity of the NP-1-/- embryo in vitro and in vivo. Here we show that NP-1 is expressed by CD45+ hematopoietic cells in the fetal liver, can bind VEGF165, and phosphorylates VEGFR-2 on endothelial cells. CD45+NP-1+ cells rescued the defective vasculogenesis and angiogenesis in the NP-1-/- P-Sp (para-aortic splanchnopleural mesodermal region) culture, although CD45+NP-1- cells did not. Moreover, CD45+NP-1+ cells together with VEGF165 induced angiogenesis in an in vivo Matrigel assay and cornea neovascularization assay. The extracellular domain of NP-1 consists of "a," "b," and "c" domains, and it is known that the "a" and "c" domains are necessary for dimerization of NP-1. We found that both the "a" and "c" domains are essential for such rescue of defective vascularities in the NP-1 mutant. These results suggest that NP-1 enhances vasculogenesis and angiogenesis exogenously and that dimerization of NP-1 is important for enhancing vascular development. In NP-1-/- embryos, vascular sprouting is impaired at the central nervous system (CNS) and pericardium where VEGF is not abundant, indicating that NP-1-expressing cells are required for normal vascular development.
影响因子：
10.5
作者：
Coussens, LM;Raymond, WW;Hanahan, D
通讯作者：
Hanahan, D
低温熔盐合成MoS2@CoS2异质结构以实现高效析氢反应
影响因子：
4.9
作者：
He, Song;Du, Hongfang;Huang, Wei
通讯作者：
Huang, Wei
DOI：
10.1073/pnas.040337597
发表时间：
2000-03-14
影响因子：
11.1
作者：
Gagnon, ML;Bielenberg, DR;Klagsbrun, M
通讯作者：
Klagsbrun, M