Pigment epithelium-derived factor exerts opposite effects on endothelial cells of different phenotypes.
The anti-angiogenic activity of pigment epithelium-derived factor (PEDF) has recently been discovered on the basis of its inhibition of ischemia-induced retinal neovascularization in an animal model of retinopathy of the premature. Moreover PEDF inhibits the migration and proliferation of various endothelial cells maintained in culture with FGF(2). Since vascular endothelial growth factor (VEGF) is the main angiogenic factor expressed in hypervascularized retinas, we investigated the functions of PEDF on retinal endothelial cells whose angiogenic phenotype is controlled or not by long term exposure to VEGF as observed in human pathologies such as diabetic retinopathy. Here, we observed that PEDF exerts opposite effects on endothelial cells depending on their phenotype. We determined that when PEDF inhibits endothelial cell growth, it inhibits VEGF-induced MAPK activation. However, in endothelial cells cultured with VEGF, PEDF has a synergistic action on cell proliferation with VEGF, and this corresponds to increased MAPK activation.
Hutchings
Helen
H
GDR CNRS 1927-Angiogenese and Institut de Pharmacologie et Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, Toulouse Cedex 31077, France.
Maitre-Boube
Martine
M
Tombran-Tink
Joyce
J
Plouët
Jean
J
D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004727:Endothelium / Q000166:cytology*; D005136:Eye Proteins; D006801:Humans; D000860:Hypoxia; D008222:Lymphokines / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009389:Neovascularization, Pathologic; D009414:Nerve Growth Factors; D010641:Phenotype; D010766:Phosphorylation; D011233:Precipitin Tests; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology*; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000737:chemistry* / Q000494:pharmacology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor
D016228:Endothelial Growth Factors; D005136:Eye Proteins; D008222:Lymphokines; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009414:Nerve Growth Factors; D011506:Proteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor