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.
Midwood
Kim S
KS
Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
Valenick
Leyla V
LV
Hsia
Henry C
HC
Schwarzbauer
Jean E
JE
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