Decorin modulates fibrin assembly and structure

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

研究成果: 雜誌貢獻文章

32 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)38208-38216
頁數9
期刊Journal of Biological Chemistry
281
發行號50
DOIs
出版狀態已發佈 - 十二月 15 2006

指紋

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

引用此文

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

於: Journal of Biological Chemistry, 卷 281, 編號 50, 15.12.2006, p. 38208-38216.

研究成果: 雜誌貢獻文章

Dugan, TA, Yang, VWC, McQuillan, DJ & Höök, M 2006, 'Decorin modulates fibrin assembly and structure', Journal of Biological Chemistry, 卷 281, 編號 50, 頁 38208-38216. https://doi.org/10.1074/jbc.M607244200
Dugan, Tracey A. ; Yang, Vivian W C ; McQuillan, David J. ; Höök, Magnus. / Decorin modulates fibrin assembly and structure. 於: Journal of Biological Chemistry. 2006 ; 卷 281, 編號 50. 頁 38208-38216.
@article{283eefc395c14dfeb45903d07d520f3c,
title = "Decorin modulates fibrin assembly and structure",
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 H{\"o}{\"o}k, 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.",
author = "Dugan, {Tracey A.} and Yang, {Vivian W C} and McQuillan, {David J.} and Magnus H{\"o}{\"o}k",
year = "2006",
month = "12",
day = "15",
doi = "10.1074/jbc.M607244200",
language = "English",
volume = "281",
pages = "38208--38216",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "50",

}

TY - JOUR

T1 - Decorin modulates fibrin assembly and structure

AU - Dugan, Tracey A.

AU - Yang, Vivian W C

AU - McQuillan, David J.

AU - Höök, Magnus

PY - 2006/12/15

Y1 - 2006/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33846002042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846002042&partnerID=8YFLogxK

U2 - 10.1074/jbc.M607244200

DO - 10.1074/jbc.M607244200

M3 - Article

C2 - 17046817

AN - SCOPUS:33846002042

VL - 281

SP - 38208

EP - 38216

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 50

ER -