Relative effects of VEGF-A and VEGF-C on endothelial cell proliferation, migration, and PAF synthesis: Role of neuropilin-1
Relative effects of VEGF-A and VEGF-C on endothelial cell proliferation, migration, and PAF synthesis: Role of neuropilin-1
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DOI：
10.1002/jcb.10155
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发表时间：
2002-01-01
影响因子：
4
通讯作者：
Sirois, MG
中科院分区：
文献类型：
--
作者：
Bernatchez, PN;Rollin, S;Sirois, MG
血管内皮生长因子（VEGF-A）是内皮细胞TO增殖、迁移和炎性物质如血小板活化因子WAIF的合成的诱导剂。最近，神经纤毛蛋白-1（NRP-1）已被描述为KDR的辅助受体，其增强VEGF-A活性。然而，NRP-1在许多VEGF-A活性中的作用仍不清楚。为了评估NRP-1对VEGF-A介导的EC增殖、迁移和PAF合成的贡献，我们使用重组表达Fit-1、NRP-1、KDR或KDR和NRP-1的猪主动脉EC（PAEC）。用结合Flt-1、KDR和NRP-1的VEGF-A和仅结合KDR的VEGF-C刺激细胞。VEGF-A在PAEC-KDR中诱导KDR磷酸化的效力是VEGF-C的12.4倍。VEGF-A和VEGF-C在介导PAEC-KDR增殖、迁移和PAF合成方面表现出相似的效力。在PAEC-KDR/NRP-1上，VEGF-A在诱导KDR磷酸化和PAEC-KDR/NRP-1增殖（1.3倍）、迁移（1.7倍）和PAF合成（4.6倍）方面的效力是VEGF-C的28.6倍。这些结果表明VEGF-A与KDR和NRP-1的协同结合增强了KDR磷酸化及其生物活性。用内源性表达KDR和NRP-1受体的牛主动脉EC获得了类似的结果。相反，用VEGF-A或VEGF-C刺激PAEC-Flt-1和PAEC-NRP-1不会诱导增殖、迁移或PAF合成。总之，EC上NRP-1的存在优先增加VEGF-A对KDR的激活以及KDR介导的生物活性，并可能引发新的细胞内事件。另一方面，VEGF-A和VEGF-C在不存在NRP-1的情况下对EC具有等效的生物活性。
Vascular endothelial growth factor (VEGF-A) is an inducer of endothelial cell TO proliferation, migration, and synthesis of inflammatory agents such as platelet-activating factor WAIF). Recently, neuropilin-1 (NRP-1) has been described as a coreceptor of KDR which potentiates VEGF-A activity. However, the role of NRP-1 in numerous VEGF-A activities remains unclear. To assess the contribution of NRP-1 to VEGF-A mediated EC proliferation, migration, and PAF synthesis, we used porcine aortic EC (PAEC) recombinantly expressing Fit-1, NRP-1, KDR or KDR and NRP-1. Cells were stimulated with VEGF-A, which binds to Flt-1, KDR and NRP-1, and VEGF-C, which binds to KDR only. VEGF-A was 12.4-fold more potent than VEGF-C in inducing KDR phosphorylation in PAEC-KDR. VEGF-A and VEGF-C showed similar potency to mediate PAEC-KDR proliferation, migration, and PAF synthesis. On PAEC-KDR/NRP-1, VEGF-A was 28.6-fold more potent than VEGF-C in inducing KDR phosphorylation and PAEC-KDR/NRP-1 proliferation ((1.3-fold), migration (1.7-fold), and PAF synthesis (4.6-fold). These results suggest that cooperative binding of VEGF-A to KDR and NRP-1 enhances KDR phosphorylation and its biological activities. Similar results were obtained with bovine aortic EC that endogenously express both KDR and NRP-1 receptors. In contrast, stimulation of PAEC-Flt-1 and PAEC-NRP-1 with VEGF-A or VEGF-C did not induce proliferation, migration, or PAF synthesis. In conclusion, the presence of NRP-1 on EC preferentially increases KDR activation by VEGF-A as well as KDR-mediated biological activities, and may elicit novel intracellular events. On the other hand, VEGF-A and VEGF-C have equipotent biological activities on EC in absence of NRP-1.