Relationship between prostaglandin E2 and vascular endothelial growth factor (VEGF) in angiogenesis in human vascular endothelial cells.
To address the role of prostaglandin E2 (PGE2) in tube formation of endothelial cells and the relationships between the action of PGE2 and vascular endothelial growth factor (VEGF), cultured human umbilical vein endothelial cells (HUVECs) were used to evaluate tube formation on Matrigel and the expression of angiogenesis-related genes. PGE2 treatment stimulated the tube-like formation of HUVECs. Whereas VEGF-induced tube formation was significantly suppressed by ETYA, an inhibitor of arachidonic acid metabolism, or SU5614, an inhibitor of VEGF-receptor tyrosine kinase, the stimulatory effect of PGE2 was observed in the presence of ETYA or SU5614. Thus, PGE2 counteracted both ETYA- and SU5614-induced blockage of angiogenesis in the presence of VEGF. VEGF induced cyclooxygenase (COX) -2 mRNA expression in HUVECs and increased the PGE2 concentration in the medium. PGE2 treatment enhanced the expression of VEGF mRNA. These findings suggest that PGE2 directly stimulates angiogenesis, apart from VEGF signaling, and further induces VEGF expression in HUVECs. In addition, the effect of VEGF on angiogenesis may be mediated, in part, by PGE2 secretion.
Tamura
Kazuhiro
K
Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Science, Horinouchi 1432-1, Hachioji, Tokyo, 192-0392, Japan. hiro@ps.toyaku.ac.jp
Sakurai
Toshihiro
T
Kogo
Hiroshi
H
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D005786:Gene Expression Regulation; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D007797:Laminin; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic; D000071876:Prostaglandin-E Synthases; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D004338:Drug Combinations; D007797:Laminin; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D015117:5,8,11,14-Eicosatetraynoic Acid; C059485:matrigel; D003094:Collagen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone