Decorin modulates fibrin assembly and structure

Tracey A. Dugan, Vivian W.C. Yang, David J. McQuillan, Magnus Hook

    Research output: Contribution to journalArticlepeer-review

    39 Scopus citations

    Abstract

    Emerging evidence indicates that fibrin clotting is regulated by different external factors. We demonstrated recently that decorin, a regulator of collagen fibrillogenesis and transforming growth factor-β activity, binds to the D regions of fibrinogen (Dugan, T.A., Yang, V. W.-C., McQuillan, D.J., and Höök, M. (2003) J. Biol. Chem. 278, 13655-13662). We now report that the decorin-fibrinogen interaction alters the assembly, structure, and clearance of fibrin fibers. Relative to fibrinogen, substoichiometric amounts of decorin core protein modulated clotting, whereas an excess of an active decorin peptide was necessary for similar activity. These concentration-dependent effects suggest that decorin bound to the D regions sterically modulates fibrin assembly. Scanning electron microscopy images of fibrin clotted in the presence of increasing concentrations of decorin core protein showed progressively decreasing fiber diameter. The sequestration of Zn2+ ions from the N-terminal fibrinogen-binding region abrogated decorin incorporation into the fibrin network. Compared with linear thicker fibrin fibers, the curving thin fibers formed with decorin underwent accelerated tissue-type plasminogen activator-dependent fibrinolysis. Collectively, these data demonstrate that decorin can regulate fibrin organization and reveal a novel mechanism by which extracellular matrix components can participate in hemostasis, thrombosis, and wound repair.

    Original languageEnglish (US)
    Pages (from-to)38208-38216
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume281
    Issue number50
    DOIs
    StatePublished - Dec 15 2006

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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