Decorin modulates fibrin assembly and structure

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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
Pages (from-to)38208-38216
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number50
DOIs
Publication statusPublished - Dec 15 2006

Fingerprint

Decorin
Fibrin
Fibrinogen
D region
Fibers
Transforming Growth Factors
Fibrinolysis
Tissue Plasminogen Activator
Hemostasis
Electron Scanning Microscopy
Extracellular Matrix
Proteins
Thrombosis
Repair
Collagen
Ions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Decorin modulates fibrin assembly and structure. / Dugan, Tracey A.; Yang, Vivian W C; McQuillan, David J.; Höök, Magnus.

In: Journal of Biological Chemistry, Vol. 281, No. 50, 15.12.2006, p. 38208-38216.

Research output: Contribution to journalArticle

Dugan, Tracey A. ; Yang, Vivian W C ; McQuillan, David J. ; Höök, Magnus. / Decorin modulates fibrin assembly and structure. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 50. pp. 38208-38216.
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