Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z
Department of Biology, Technion, Israel Institute of Technology, Technion City, Haifa 32000, Israel.
FASEB J. 1999 Jan;13(1):9-22.
Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells. Five VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene. These isoforms differ in their molecular mass and in biological properties such as their ability to bind to cell-surface heparan-sulfate proteoglycans. The expression of VEGF is potentiated in response to hypoxia, by activated oncogenes, and by a variety of cytokines. VEGF induces endothelial cell proliferation, promotes cell migration, and inhibits apoptosis. In vivo VEGF induces angiogenesis as well as permeabilization of blood vessels, and plays a central role in the regulation of vasculogenesis. Deregulated VEGF expression contributes to the development of solid tumors by promoting tumor angiogenesis and to the etiology of several additional diseases that are characterized by abnormal angiogenesis. Consequently, inhibition of VEGF signaling abrogates the development of a wide variety of tumors. The various VEGF forms bind to two tyrosine-kinase receptors, VEGFR-1 (flt-1) and VEGFR-2 (KDR/flk-1), which are expressed almost exclusively in endothelial cells. Endothelial cells express in addition the neuropilin-1 and neuropilin-2 coreceptors, which bind selectively to the 165 amino acid form of VEGF (VEGF165). This review focuses on recent developments that have widened considerably our understanding of the mechanisms that control VEGF production and VEGF signal transduction and on recent studies that have shed light on the mechanisms by which VEGF regulates angiogenesis.
血管内皮生长因子（VEGF）是一种高度特异性的血管内皮细胞有丝分裂原。单个VEGF基因通过可变剪接产生五种VEGF异构体。这些异构体的分子量和生物学特性不同，例如它们与细胞表面硫酸乙酰肝素蛋白聚糖结合的能力。VEGF的表达在缺氧、激活的癌基因以及多种细胞因子的作用下增强。VEGF诱导内皮细胞增殖，促进细胞迁移，并抑制细胞凋亡。在体内，VEGF诱导血管生成以及血管通透性增加，并在血管发生的调节中起核心作用。VEGF表达失调通过促进肿瘤血管生成导致实体瘤的发展，并导致其他几种以异常血管生成为特征的疾病的病因。因此，抑制VEGF信号传导可消除多种肿瘤的发展。各种VEGF形式与两种酪氨酸激酶受体VEGFR-1（flt-1）和VEGFR-2（KDR/flk-1）结合，这两种受体几乎只在内皮细胞中表达。内皮细胞还表达神经纤毛蛋白-1和神经纤毛蛋白-2共受体，它们选择性地结合VEGF的165个氨基酸形式（VEGF165）。本综述重点关注最近的进展，这些进展大大拓宽了我们对控制VEGF产生和VEGF信号转导机制的理解，以及最近的研究，这些研究揭示了VEGF调节血管生成的机制。
