Type I, II, III, IV, V, and VI collagens serve as extracellular ligands for the isoforms of platelet-derived growth factor (AA, BB, and AB).
The biological activities of several growth factors/cytokines have been shown to be modulated by binding to molecules of the extracellular matrix. Here, the interactions of PDGF (isoforms AA, BB, and AB), a potent mitogen for mesenchymal cells, with collagens were investigated. All radiolabeled PDGF isoforms specifically interacted with type I, II, III, IV, V, and VI collagens (preferential binding to types III, I, VI, and IV) and their constituent chains, either when immobilized on polystyrene or blotted to nitrocellulose. PDGF-collagen interactions were of medium affinity (KD between 4 and 22 nM) and were inhibited by different soluble collagen chains suggesting a collagenous consensus binding site(s) for the PDGF isoforms investigated. Scatchard analysis revealed molar ratios of up to 3-4 PDGF molecules bound/triple-helical (native) collagen. Biological activity of collagen-bound PDGF was demonstrated by a 1.5-3-fold stimulation of proliferation of human fibroblasts and mouse 3T3 cells. Furthermore, a preferential association of PDGF with the collagenous extracellular matrix of cirrhotic liver could be shown by immunostaining. Our data are in accord with previous studies that localized PDGF in the extracellular matrix of fibroproliferative lesions and suggest that binding of PDGF to collagens may localize and modulate its biological activities.
Abteilung für Gastroenterologie und Hepatologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.
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Somasundaram
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Schuppan
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D003094:Collagen / Q000276:immunology / Q000378:metabolism*; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D008024:Ligands; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
D000939:Epitopes; D008024:Ligands; D010982:Platelet-Derived Growth Factor; D003094:Collagen