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

Nature Medicine volume 4, pages 691–697 (1998)Cite this article

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.

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Author notes

  1. Masato Kato

    Present address: Hematology/Immunology/Transfusion Medicine Research Group, Christchurch School of Medicine, Christchurch, New Zealand

  2. Huiming Wang

    Present address: Trancell Technologies, Inc., Monmouth Junction, NJ 08825

Authors and Affiliations

  1. Department of Pediatrics, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115

    Masato Kato, Huiming Wang, Varpu Kainulainen, Marilyn L. Fitzgerald & Merton Bernfield

  2. Genzyme Corporation, 1 Mountain Road, Framingham, Massachusetts, 01710

    Steven Ledbetter

  3. Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri, 63110

    David M. Ornitz

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Kato, M., Wang, H., Kainulainen, V. et al. Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2. Nat Med 4, 691–697 (1998). https://doi.org/10.1038/nm0698-691

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