Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2

Masato Kato, Huiming Wang, Varpu Kainulainen, Marilyn L. Fitzgerald, Steven Ledbetter, David M. Ornitz, Merton Bernfield

Research output: Contribution to journalArticle

269 Scopus citations

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.

Original languageEnglish
Pages (from-to)691-697
Number of pages7
JournalNature medicine
Volume4
Issue number6
DOIs
StatePublished - Jun 1 1998

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