PHYSIOLOGICAL DEGRADATION CONVERTS THE SOLUBLE SYNDECAN-1 ECTODOMAIN FROM AN INHIBITOR TO A POTENT ACTIVATOR OF FGF-2

The activity of fibroblast growth factor 2 (FGF-2) is stringently cont rolled. Inactive in undisturbed tissues, it is activated during injury and is critical for tissue repair. We find that this control can be i mposed by the soluble syndecan-1 ectodomain, a heparan sulfate proteog lycan shed from cell surfaces into wound fluids. The ectodomain potent ly inhibits heparin-mediated FGF-2 mitogenicity because of the poorly sulfated domains in its heparin sulfate chains. Degradation of these r egions by platelet heparanase produces heparin-like heparin sulfate fr agments that markedly activate FCF-2 mitogenicity and are found in wou nd fluids. These results establish a novel physiological control for F GF-2 and suggest new ways to modulate FGF activity.