Premium
Relative effects of VEGF‐A and VEGF‐C on endothelial cell proliferation, migration and PAF synthesis: Role of neuropilin‐1
Author(s) -
Bernatchez Pascal N.,
Rollin Simon,
Soker Shay,
Sirois Martin G.
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10155
Subject(s) - neuropilin 1 , phosphorylation , kinase insert domain receptor , vascular endothelial growth factor , chemistry , cell migration , cell growth , receptor , growth factor , vegf receptors , microbiology and biotechnology , endocrinology , vascular endothelial growth factor a , medicine , cancer research , cell , biology , biochemistry
Abstract Vascular endothelial growth factor (VEGF‐A) is an inducer of endothelial cell (EC) proliferation, migration, and synthesis of inflammatory agents such as platelet‐activating factor (PAF). 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 Flt‐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. J. Cell. Biochem. 85: 629–639, 2002. © 2002 Wiley‐Liss, Inc.