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

Kim S. Midwood, Leyla V. Valenick, Henry C. Hsia, Jean E. Schwarzbauer

Research output: Contribution to journalArticle

96 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5670-5677
Number of pages8
JournalMolecular biology of the cell
Volume15
Issue number12
DOIs
StatePublished - Dec 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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