Vascular Endothelial Growth Factor KDR Receptor Signaling Potentiates Tumor Necrosis Factor-induced Tissue Factor Expression in Endothelial Cells *

摘要: Vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-alpha) have been shown to synergistically increase tissue (TF) expression in cells; however, the role of VEGF receptors (KDR, Flt-1, neuropilin) this process is unclear. Here we report that binding KDR receptor necessary sufficient for potentiation TNF-induced TF human umbilical vein cells. was evaluated by Western blot analysis fluorescence-activated cell sorting. In absence TNF-alpha, wild-type VEGF- or receptor-selective variants induced an approximate 7-fold total expression. Treatment with TNF alone produced 110-fold expression, whereas coincubation TNF-alpha KDR-selective resulted 250-fold lacking heparin domain also able potentiate indicating heparin-sulfate proteoglycan neuropilin not required up-regulation. Neither placental nor Flt-1-selective variant capable inducing presence TNF. Inhibition protein-tyrosine kinase protein C activity significantly blocked TNF/VEGF up-regulation, phorbol 12-myristate 13-acetate, a activator, increased These data demonstrate signaling governs both VEGF-induced up-regulation TF.