Aitkenhead M, Christ B, Eichmann A, Feucht M, Wilson D J, Wilting J
School of Biomedical Science/Anatomy, The Queen's University of Belfast, Northern Ireland.
Dev Dyn. 1998 May;212(1):1-13. doi: 10.1002/(SICI)1097-0177(199805)212:1<1::AID-AJA1>3.0.CO;2-L.
The expression of vascular endothelial growth factor (VEGF) has been described to coincide both temporally and spatially with angiogenesis suggesting a role as a paracrine stimulator of endothelial cells. We have used digoxigenin labelled RNA probes to VEGF and the VEGF receptor-2 (Quek1) to investigate the relationship between VEGF expression and vascular events in quail embryos from day 1 to 13 of incubation. Furthermore, the effect of exogenously applied VEGF was studied in day 4 quail embryos using polyclonal anti-VEGF antibodies. Expression of VEGF mRNA was observed in day 1 and 2 embryos in regions of active angiogenesis and hemangiopoiesis. VEGF mRNA expression was found at high levels in the ventral aspect of the neural tube and Quek1 mRNA expression in the accompanying endothelial cells of day 3 embryos, suggesting a function in brain angiogenesis. However, in the neural tube, thyroid gland and cartilaginous skeleton VEGF mRNA was expressed at least 1 day before the ingrowth of vessels, suggesting that additional mechanisms are involved in control of angiogenesis. This is supported by the observation that application of VEGF165 into the midbrain induced dilatation of perineural vessels, while the intraneural vessels remained almost unaffected. Expression of VEGF mRNA was also observed at high levels in podocytes during all stages, indicative of its importance in glomerular development and function. The results of the present study indicate that as angiogenesis occurred in other tissues and organs (day 13 metanephros, dorsal third of the day 7 neural tube, skeletal muscle, and many mesodermal compartments), there was concurrent paracrine expression of VEGF mRNA and Quek1 mRNA. One noteable exception was the hepatocytes of the developing liver which appeared to remain VEGF-negative throughout the study. However, a small number of endothelial cells within liver sinuses, and additionally within the kidney and the elastic arteries, expressed VEGF mRNA. These results suggest that VEGF may also act as an autocrine mediator of angiogenesis, possibly as a result of localised tissue hypoxia.
血管内皮生长因子（VEGF）的表达在时间和空间上均与血管生成同步，这表明其作为内皮细胞旁分泌刺激因子发挥作用。我们使用地高辛标记的针对VEGF和VEGF受体-2（Quek1）的RNA探针，来研究孵化第1天至13天鹌鹑胚胎中VEGF表达与血管事件之间的关系。此外，使用多克隆抗VEGF抗体，在第4天鹌鹑胚胎中研究了外源性应用VEGF的效果。在活跃血管生成和血管造血区域的第1天和第2天胚胎中观察到VEGF mRNA的表达。在第3天胚胎神经管腹侧发现VEGF mRNA高水平表达，而在伴随的内皮细胞中发现Quek1 mRNA表达，提示其在脑血管生成中的作用。然而，在神经管、甲状腺和软骨骨骼中，VEGF mRNA在血管长入前至少1天就已表达，这表明血管生成的控制涉及其他机制。向中脑应用VEGF165可诱导神经周血管扩张，而神经内血管几乎不受影响，这一观察结果支持了上述观点。在所有阶段的足细胞中也观察到VEGF mRNA的高水平表达，表明其在肾小球发育和功能中的重要性。本研究结果表明，随着其他组织和器官发生血管生成（第13天的后肾、第7天神经管背侧三分之一、骨骼肌和许多中胚层隔室），同时存在VEGF mRNA和Quek1 mRNA的旁分泌表达。一个明显的例外是发育中的肝脏的肝细胞，在整个研究过程中似乎一直呈VEGF阴性。然而，肝窦内以及肾脏和弹性动脉内的少数内皮细胞表达VEGF mRNA。这些结果表明，VEGF也可能作为血管生成的自分泌介质，可能是局部组织缺氧的结果。
