The chemotactic and mitogenic effects of platelet-derived growth factor-BB on rat aorta smooth muscle cells are inhibited by basic fibroblast growth factor.
In response to endovascular injury, platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF) are released locally and modulate vascular smooth muscle cells (SMC) proliferation and migration within the vascular wall. The aim of the present in vitro study was to determine how rat aorta SMC respond to the simultaneous exposure to PDGF-BB and bFGF. In a modified Boyden chamber assay bFGF exhibited a dose-dependent effect to inhibit the chemotactic action of PDGF-BB. A comparable result was observed in proliferation assays. In contrast, MIP-1 beta, epidermal growth factor (EGF), fibronectin and acidic FGF (aFGF) did not inhibit the chemotactic effect of PDGF-BB. Denatured bFGF did not exert an inhibitory effect and neutralizing antibodies either to bFGF or to bFGF-receptor abolished the inhibition observed in the presence of bFGF. The role played by PDGF receptor alpha (PDGF-Ralpha) was investigated in PDGF-Ralpha-dominant negative-transfected SMC, by selectively blocking PDGF-BB-binding to PDGF-Ralpha with neomycin, by neutralizing PDGF-Ralpha with a monoclonal antibody and by selectively stimulating PDGF-Ralpha with PDGF-AA; in all cases the effect of bFGF to inhibit PDGF-BB-directed SMC migration was abolished. These in vitro studies show that bFGF significantly inhibits PDGF-BB-induced SMC migration and proliferation and that this effect is mediated by both PDGF-Ralpha and bFGF receptor.
Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. a.facchiano@idi.it
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Facchiano
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De Marchis
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Turchetti
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Facchiano
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Guglielmi
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Denaro
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Palumbo
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Scoccianti
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Capogrossi
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D009355:Neomycin / Q000494:pharmacology; D009500:Neutralization Tests; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000906:Antibodies; D010982:Platelet-Derived Growth Factor; D011500:Protein Synthesis Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor; D009355:Neomycin