Abstract
The activity of fibroblast growth factor 2 (FGF-2) is stringently controlled. Inactive in undisturbed tissues, it is activated during injury and is critical for tissue repair. We find that this control can be imposed by the soluble syndecan-1 ectodomain, a heparan sulfate proteoglycan shed from cell surfaces into wound fluids. The ectodomain potently inhibits heparin-mediated FGF-2 mitogenicity because of the poorly sulfated domains in its heparin sulfate chains. Degradation of these regions by platelet heparanase produces heparin-like heparin sulfate fragments that markedly activate FGF-2 mitogenicity and are found in wound fluids. These results establish a novel physiological control for FGF-2 and suggest new ways to modulate FGF activity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites / physiology
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Exudates and Transudates / chemistry
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Exudates and Transudates / metabolism
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Fibrinolytic Agents / pharmacology
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Fibroblast Growth Factor 2 / antagonists & inhibitors
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Fibroblast Growth Factor 2 / drug effects
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Fibroblast Growth Factor 2 / metabolism*
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Glucuronidase*
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Glycoside Hydrolases / pharmacology
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Heparin / pharmacology
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Heparitin Sulfate / metabolism
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Humans
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Membrane Glycoproteins / drug effects
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Membrane Glycoproteins / metabolism*
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Mitogens / metabolism
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Oligosaccharides / pharmacology
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Protein Binding
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Proteoglycans / drug effects
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Proteoglycans / metabolism*
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Receptor Protein-Tyrosine Kinases*
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor / metabolism
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Solubility
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Syndecan-1
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Syndecans
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Wounds and Injuries / metabolism
Substances
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Fibrinolytic Agents
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Membrane Glycoproteins
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Mitogens
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Oligosaccharides
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Proteoglycans
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Receptors, Fibroblast Growth Factor
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SDC1 protein, human
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Syndecan-1
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Syndecans
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Fibroblast Growth Factor 2
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Heparin
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Heparitin Sulfate
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FGFR1 protein, human
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Glycoside Hydrolases
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heparanase
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Glucuronidase