Home LiteratureArticle Details
PMID: 15483051 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Coregulation of fibronectin signaling and matrix contraction by tenascin-C and syndecan-4.

Molecular biology of the cell ·Vol. 15 ·No. 12 ·2004-12-00 ·Pages 5670-7

Midwood KS, Valenick LV, Hsia HC, Schwarzbauer JE

Abstract

Syndecan-4 is a ubiquitously expressed heparan sulfate proteoglycan that modulates cell interactions with the extracellular matrix. It is transiently up-regulated during tissue repair by cells that mediate wound healing. Here, we report that syndecan-4 is essential for optimal fibroblast response to the three-dimensional fibrin-fibronectin provisional matrix that is deposited upon tissue injury. Interference with syndecan-4 function inhibits matrix contraction by preventing cell spreading, actin stress fiber formation, and activation of focal adhesion kinase and RhoA mediated-intracellular signaling pathways. Tenascin-C is an extracellular matrix protein that regulates cell response to fibronectin within the provisional matrix. Syndecan-4 is also required for tenascin-C action. Inhibition of syndecan-4 function suppresses tenascin-C activity and overexpression of syndecan-4 circumvents the effects of tenascin-C. In this way, tenascin-C and syndecan-4 work together to control fibroblast morphology and signaling and regulate events such as matrix contraction that are essential for efficient tissue repair.

MeSH Terms
Animals Cell Line Cricetinae DNA, Complementary/genetics Extracellular Matrix/drug effects,metabolism Fibrin/metabolism Fibronectins/metabolism Membrane Glycoproteins/deficiency,genetics,metabolism Mice Mice, Knockout Proteoglycans/deficiency,genetics,metabolism Rats Signal Transduction Syndecan-4 Tenascin/metabolism rhoA GTP-Binding Protein/metabolism
Chemicals
DNA, Complementary Fibronectins Membrane Glycoproteins Proteoglycans Sdc4 protein, mouse Sdc4 protein, rat Syndecan-4 Tenascin Fibrin rhoA GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Midwood Kim S
Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
Valenick Leyla V
Hsia Henry C
Schwarzbauer Jean E
References (42)
42 references, click to expand
  1. Tenascin interferes with fibronectin action.
    Cell. 1988 May 6;53(3):383-90 PMID: 2452695
  2. Animal cell mutants defective in glycosaminoglycan biosynthesis.
    Proc Natl Acad Sci U S A. 1985 May;82(10):3197-201 PMID: 3858816
  3. Undersulfated heparan sulfate in a Chinese hamster ovary cell mutant defective in heparan sulfate N-sulfotransferase.
    J Biol Chem. 1989 May 15;264(14):8059-65 PMID: 2524478
  4. Syndecan from embryonic tooth mesenchyme binds tenascin.
    J Biol Chem. 1991 Apr 25;266(12):7733-9 PMID: 1708391
  5. Localization of the major heparin-binding site in fibronectin.
    J Biol Chem. 1991 Apr 25;266(12):7812-8 PMID: 2019604
  6. Genetic analysis of proteoglycan structure, function and metabolism.
    Curr Opin Cell Biol. 1991 Oct;3(5):805-16 PMID: 1931081
  7. The alternatively spliced V region contributes to the differential incorporation of plasma and cellular fibronectins into fibrin clots.
    J Cell Biol. 1992 Nov;119(4):923-33 PMID: 1358897
  8. Accumulation of a pentasaccharide terminating in alpha-N-acetylglucosamine in an animal cell mutant defective in heparan sulfate biosynthesis.
    J Biol Chem. 1995 May 26;270(21):12557-62 PMID: 7759502
  9. An animal cell mutant defective in heparan sulfate hexuronic acid 2-O-sulfation.
    J Biol Chem. 1996 Jul 26;271(30):17711-7 PMID: 8663454
  10. Changes in cell spreading and cytoskeletal organization are induced by adhesion to a fibronectin-fibrin matrix.
    Blood. 1996 Jul 1;88(1):158-66 PMID: 8704170
  11. Syndecans-1 and -4 are induced during wound repair of neonatal but not fetal skin.
    J Invest Dermatol. 1996 Nov;107(5):676-83 PMID: 8875948
  12. Tenascin-C promotes healing of Habu-snake venom-induced glomerulonephritis: studies in knockout congenic mice and in culture.
    Am J Pathol. 1998 May;152(5):1237-45 PMID: 9588892
  13. ECM signalling: orchestrating cell behaviour and misbehaviour.
    Trends Cell Biol. 1998 Nov;8(11):437-41 PMID: 9854310
  14. Cooperative role for activated alpha4 beta1 integrin and chondroitin sulfate proteoglycans in cell adhesion to the heparin III domain of fibronectin. Identification of a novel heparin and cell binding sequence in repeat III5.
    J Biol Chem. 1999 Jan 1;274(1):135-42 PMID: 9867821
  15. Proteoglycans: master regulators of molecular encounter?
    Matrix Biol. 1998 Nov;17(7):465-72 PMID: 9881597
  16. Syndecan-4 signals cooperatively with integrins in a Rho-dependent manner in the assembly of focal adhesions and actin stress fibers.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2805-10 PMID: 10077592
  17. Fibronectin regulates assembly of actin filaments and focal contacts in cultured cells via the heparin-binding site in repeat III13.
    Mol Biol Cell. 1999 May;10(5):1521-36 PMID: 10233160
  18. Requirements for alpha(5)beta(1) integrin-mediated retraction of fibronectin-fibrin matrices.
    J Biol Chem. 1999 Jul 23;274(30):20943-8 PMID: 10409640
  19. Syndecan-4 binding to the high affinity heparin-binding domain of fibronectin drives focal adhesion formation in fibroblasts.
    Arch Biochem Biophys. 2000 Feb 1;374(1):66-72 PMID: 10640397
  20. Syndecan-4 deficiency impairs focal adhesion formation only under restricted conditions.
    J Biol Chem. 2000 Feb 25;275(8):5249-52 PMID: 10681494
  21. Participation of syndecan 2 in the induction of stress fiber formation in cooperation with integrin alpha5beta1: structural characteristics of heparan sulfate chains with avidity to COOH-terminal heparin-binding domain of fibronectin.
    Exp Cell Res. 2000 May 1;256(2):434-44 PMID: 10772816
  22. Integrin modulation by lateral association.
    J Biol Chem. 2000 Aug 11;275(32):24233-6 PMID: 10801896
  23. Tenascin-C suppresses Rho activation.
    J Cell Biol. 2000 Aug 21;150(4):913-20 PMID: 10953015
  24. Tenascin-C in development and disease: gene regulation and cell function.
    Matrix Biol. 2000 Dec;19(7):581-96 PMID: 11102748
  25. Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4.
    J Clin Invest. 2001 Jan;107(2):R9-R14 PMID: 11160142
  26. Identification of a novel heparin-binding site in the alternatively spliced IIICS region of fibronectin: roles of integrins and proteoglycans in cell adhesion to fibronectin splice variants.
    Matrix Biol. 2001 Feb;20(1):63-73 PMID: 11246004
  27. Syndecan-4 deficiency increases susceptibility to kappa-carrageenan-induced renal damage.
    Lab Invest. 2001 Apr;81(4):509-16 PMID: 11304570
  28. Thrombospondins as matricellular modulators of cell function.
    J Clin Invest. 2001 Apr;107(8):929-34 PMID: 11306593
  29. Syndecan-4 as antithrombin receptor of human neutrophils.
    Biochem Biophys Res Commun. 2001 Sep 14;287(1):42-6 PMID: 11549250
  30. Taking cell-matrix adhesions to the third dimension.
    Science. 2001 Nov 23;294(5547):1708-12 PMID: 11721053
  31. Interference of tenascin-C with syndecan-4 binding to fibronectin blocks cell adhesion and stimulates tumor cell proliferation.
    Cancer Res. 2001 Dec 1;61(23):8586-94 PMID: 11731446
  32. Regulatory role for SRC and phosphatidylinositol 3-kinase in initiation of fibronectin matrix assembly.
    J Biol Chem. 2002 May 31;277(22):19703-8 PMID: 11912200
  33. Preparation and analysis of synthetic multicomponent extracellular matrix.
    Methods Cell Biol. 2002;69:145-61 PMID: 12070990
  34. Syndecan-4 modulates focal adhesion kinase phosphorylation.
    J Biol Chem. 2002 Sep 6;277(36):32970-7 PMID: 12087088
  35. Tenascin-C modulates matrix contraction via focal adhesion kinase- and Rho-mediated signaling pathways.
    Mol Biol Cell. 2002 Oct;13(10):3601-13 PMID: 12388760
  36. Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling.
    Biochem J. 2002 Nov 15;368(Pt 1):1-15 PMID: 12241528
  37. Fibroblast biology in three-dimensional collagen matrices.
    Trends Cell Biol. 2003 May;13(5):264-9 PMID: 12742170
  38. Tenascin-C blocks cell-cycle progression of anchorage-dependent fibroblasts on fibronectin through inhibition of syndecan-4.
    Oncogene. 2003 Jun 19;22(25):3917-26 PMID: 12813465
  39. Tenascins: regulation and putative functions during pathological stress.
    J Pathol. 2003 Jul;200(4):488-99 PMID: 12845616
  40. Heparan sulfate proteoglycans are involved in opiate receptor-mediated cell migration.
    Biochemistry. 2004 Jan 13;43(1):237-44 PMID: 14705951
  41. Tissue repair and the dynamics of the extracellular matrix.
    Int J Biochem Cell Biol. 2004 Jun;36(6):1031-7 PMID: 15094118
  42. Induction of tenascin in healing wounds.
    J Cell Biol. 1988 Dec;107(6 Pt 2):2757-67 PMID: 2462568
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e04-08-0759
Published
2004-12-00
Epub
2004-00-13
Pages
5670-7
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC532045
Subset
IM
Grants
NCI NIH HHS · R01 CA044627 · United States
NCI NIH HHS · CA44627 · United States
External Links
PubMed source DOI: 10.1091/mbc.e04-08-0759 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2