COORDINATE EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR RECEPTOR-1 (FLT-1) AND ITS LIGAND SUGGESTS A PARACRINE REGULATION OF MURINE VASCULAR DEVELOPMENT
COORDINATE EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR RECEPTOR-1 (FLT-1) AND ITS LIGAND SUGGESTS A PARACRINE REGULATION OF MURINE VASCULAR DEVELOPMENT
复制标题
DOI：
10.1002/aja.1002040303
复制
发表时间：
1995-11-01
影响因子：
2.5
通讯作者：
RISAU, W
中科院分区：
文献类型：
--
作者：
BREIER, G;CLAUSS, M;RISAU, W
血管内皮生长因子（VEGF）是胚胎发育和肿瘤血管生长的候选调节因子。为了评估VEGF受体-1/flt-1 （VEGFR1/flt-1）在血管系统发育中的作用，我们对人类flt-1基因的小鼠同源物进行了表征，并分析了其在小鼠胚胎发生过程中的表达模式。利用转染的COS细胞进行受体结合研究发现，小鼠flt-1基因编码VEGF高亲和力受体。通过Scatchard分析，VEGF结合的表观K-d为114 pM，表明VEGFRi/flt-1比VEGF受体2/flk-1 （VEGFR2/flk-1）对VEGF具有更高的亲和力。通过原位杂交，VEGFRi/flt-1在血管发育早期的卵黄囊中胚层中被检测到，而受体配体在7.5天的小鼠胚胎的整个内胚层中表达。与VEGFR2/flk-1的比较表明，这两种受体在卵黄囊中胚层具有共同的表达域，但在胎盘外锥体中的表达位点不同。两种VEGF受体的差异表达在发育中的胎盘中持续存在，其中VEGFR1/flt-1 mRNA在海绵滋养层中检测到，而VECFR2/flk-1转录本存在于VEGF表达的迷路层。在胚胎中，VEGFR1/flt-1 mRNA特异性定位于发育器官的血管和毛细血管中，与VEGFR2/flk-1转录本的分布模式非常相似。在发育中的大脑中，血管内皮生长因子受体在神经周围毛细血管丛和侵入神经外胚层的毛细血管芽中的表达与内皮细胞增殖和脑血管生成有关。这些数据与假设一致，即VEGF及其受体在内皮细胞谱系的分化和发育器官的新生血管形成中都具有重要功能，并以旁分泌方式起作用。(C) 1995 Wiley-Liss, Inc。
Vascular endothelial growth factor (VEGF) is a candidate regulator of blood vessel growth during embryonic development and in tumors. To evaluate the role of VEGF receptor-1/flt-1 (VEGFR1/flt-1) in the development of the vascular system, we have characterized the murine homolog of the human flt-1 gene and have analyzed its expression pattern during mouse embryogenesis. Receptor binding studies using transfected COS cells revealed that the murine flt-1 gene encodes a high affinity receptor for VEGF. The apparent K-d for VEGF binding, as determined by Scatchard analysis, was 114 pM, demonstrating that VEGFRi/flt-1 has a higher affinity to VEGF than VEGF receptor-2/flk-1 (VEGFR2/flk-1). By in situ hybridization, VEGFRi/flt-1 was detected in the yolk sac mesoderm already at the early stages of vascular development, while the receptor ligand was expressed in the entire endoderm of 7.5-day mouse embryos. A comparison with VEGFR2/flk-1 showed that the two receptors shared a common expression domain in the yolk sac mesoderm, but were expressed at different sites in the ectoplacental cone. The differential expression of the two VEGF receptors persisted in the developing placenta, where VEGFR1/flt-1 mRNA was detected in the spongiotrophoblast layer, whereas VECFR2/flk-1 transcripts were present in the labyrinthine layer which is the site of VEGF expression. In the embryo proper, VEGFR1/flt-1 mRNA was specifically localized in blood vessels and capillaries of the developing organs, closely resembling the pattern of VEGFR2/flk-1 transcript distribution. In the developing brain, the expression of VEGF receptors in the perineural capillary plexus and in capillary sprouts which have invaded the neuroectoderm correlated with endothelial cell proliferation and brain angiogenesis. The data are consistent with the hypothesis that VEGF and its receptors have an important function both in the differentiation of the endothelial lineage and in the neovascularization of developing organs, and act in a paracrine fashion. (C) 1995 Wiley-Liss, Inc.