Yang Suya, Toy Karen, Ingle Gladys, Zlot Constance, Williams P Mickey, Fuh Germaine, Li Bing, de Vos Abraham, Gerritsen Mary E
Department of Cardiovascular Research, Genentech Inc, South San Francisco, Calif, USA.
Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1797-803. doi: 10.1161/01.atv.0000038995.31179.24.
This study evaluated the relative roles of the vascular endothelial growth factor (VEGF) receptors KDR and Flt-1 in the mediation of altered gene expression elicited by VEGF.
We used mutants of VEGF selective for the KDR and Flt-1 receptors to differentiate gene expression patterns mediated by wild-type VEGF (VEGFwt) in human umbilical vein endothelial cells. RNA was extracted from cells treated for 24 hours with 1 nmol/L of each ligand, and gene expression was monitored by using oligonucleotide arrays (Affymetrix U95A). We report that activation of KDR was sufficient to upregulate all the genes induced by VEGFwt. In contrast, there were no genes selectively upregulated by the Flt-selective mutant. However, high concentrations of the Flt-selective mutant could augment the expression of some genes induced by submaximal concentrations of VEGFwt but not the KDR-selective mutant.
The binding of VEGF to its receptor, KDR, is necessary and sufficient to induce the gene expression profile induced by this growth factor. Furthermore, in human umbilical vein endothelial cells, the Flt-1 receptor appears to act as a decoy receptor, tempering the response to lower concentrations of VEGF.
本研究评估血管内皮生长因子（VEGF）受体KDR和Flt-1在介导VEGF引发的基因表达改变中的相对作用。
我们使用对KDR和Flt-1受体具有选择性的VEGF突变体，以区分野生型VEGF（VEGFwt）在人脐静脉内皮细胞中介导的基因表达模式。从用1 nmol/L每种配体处理24小时的细胞中提取RNA，并使用寡核苷酸阵列（Affymetrix U95A）监测基因表达。我们报告，KDR的激活足以上调VEGFwt诱导的所有基因。相反，没有基因被Flt选择性突变体选择性上调。然而，高浓度的Flt选择性突变体可增强由亚最大浓度的VEGFwt诱导的一些基因的表达，但不能增强KDR选择性突变体诱导的基因表达。
VEGF与其受体KDR的结合对于诱导该生长因子诱导的基因表达谱是必要且充分的。此外，在人脐静脉内皮细胞中，Flt-1受体似乎充当诱饵受体，调节对较低浓度VEGF的反应。
