Coregulation of fibronectin signaling and matrix contraction by tenascin-C and syndecan-4.
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.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
Kim S
KS
Midwood
Leyla V
LV
Valenick
Henry C
HC
Hsia
Jean E
JE
Schwarzbauer
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D053671:Syndecan-4; D019063:Tenascin / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D018076:DNA, Complementary; D005353:Fibronectins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508306:Sdc4 protein, mouse; C508307:Sdc4 protein, rat; D053671:Syndecan-4; D019063:Tenascin; D005337:Fibrin; D020742:rhoA GTP-Binding Protein