Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1.
Wound repair is a tightly regulated process stimulated by proteases, growth factors, and chemokines, which are modulated by heparan sulfate. To characterize further the role of the heparan sulfate proteoglycan syndecan-1 in wound repair, we generated mice overexpressing syndecan-1 (Snd/Snd) and studied dermal wound repair. Wound closure, reepithelialization, granulation tissue formation, and remodeling were delayed in Snd/Snd mice. Soluble syndecan-1 was increased, and shedding was prolonged in wounds from Snd/Snd mice. Excess syndecan-1 increased the elastolytic activity of wound fluids. Additionally, cells in the granulation tissue and keratinocytes at wound edges showed markedly reduced proliferation rates in Snd/Snd mice. Skin grafting experiments between Snd/Snd and control mice indicated that the slower growth rate was mainly due to a soluble factor in the Snd/Snd mouse skin. Syndecan-1 immunodepletion and further degradation experiments identified syndecan-1 ectodomain as a dominant negative inhibitor of cell proliferation. These studies indicate that shed syndecan-1 ectodomain may enhance proteolytic activity and inhibit cell proliferation during wound repair.
Elenius
Varpu
V
Department of Pediatrics, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. varpu.elenius@utu.fi
Götte
Martin
M
Reizes
Ofer
O
Elenius
Klaus
K
Bernfield
Merton
M
D000818:Animals; D001826:Body Fluids; D002455:Cell Division; D004847:Epithelial Cells / Q000166:cytology; D006097:Granulation Tissue / Q000166:cytology; D015603:Keratinocytes / Q000166:cytology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D012038:Regeneration; D012995:Solubility; D053668:Syndecan-1; D053667:Syndecans; D014945:Wound Healing
D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D010447:Peptide Hydrolases