Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its alpha receptor.
Basic fibroblast growth factor (bFGF) and platelet-derived growth factor-BB (PDGF-BB) modulate vascular wall cell function in vitro and angiogenesis in vivo. The aim of the current study was to determine how bovine aorta endothelial cells (BAECs) respond to the simultaneous exposure to PDGF-BB and bFGF. It was found that bFGF-dependent BAEC migration, proliferation, and differentiation into tubelike structures on reconstituted extracellular matrix (Matrigel) were inhibited by PDGF-BB. The role played by PDGF receptor alpha (PDGF-Ralpha) was investigated by selective stimulation with PDGF-AA, by blocking PDGF-BB-binding to PDGF-Ralpha with neomycin, or by transfecting cells with dominant-negative forms of the receptors to selectively impair either PDGF-Ralpha or PDGF-Rbeta function. In all cases, PDGF-Ralpha impairment abolished the inhibitory effect of PDGF-BB on bFGF-directed BAEC migration. In addition, PDGF-Ralpha phosphorylation was increased in the presence of bFGF and PDGF, as compared to PDGF alone, whereas mitogen-activated protein kinase phosphorylation was decreased in the presence of PDGF-BB and bFGF compared with bFGF alone. In vivo experiments showed that PDGF-BB and PDGF-AA inhibited bFGF-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane assay and that PDGF-BB inhibited bFGF-induced angiogenesis in Matrigel plugs injected subcutaneously in CD1 mice. Taken together these results show that PDGF inhibits the angiogenic properties of bFGF in vitro and in vivo, likely through PDGF-Ralpha stimulation.
De Marchis
Francesco
F
Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy.
Ribatti
Domenico
D
Giampietri
Claudia
C
Lentini
Alessandro
A
Faraone
Debora
D
Scoccianti
Marco
M
Capogrossi
Maurizio C
MC
Facchiano
Antonio
A
D000818:Animals; D001011:Aorta / Q000166:cytology; D000077214:Becaplermin; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D004336:Drug Antagonism; D004730:Endothelium, Vascular / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism* / Q000502:physiology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020928:Mitogen-Activated Protein Kinases