title: PDGF and TGF-β promote tenascin-C expression in subepithelial myofibroblasts and contribute to intestinal mucosal protection in mice.
abstract: OBJECTIVE
  Tenascin-C (TnC) is a multi-domain extracellular matrix glycoprotein that is expressed at a high level during embryogenesis but is almost absent during normal postnatal life. This multi-domain complex molecule is reported to associate with both pro-inflammatory and anti-inflammatory signalling cascades. In this study, we examined how TnC modulated intestinal inflammation.
  
  
  METHODS
  TnC pathophysiology was evaluated in cultures of rat intestinal subepithelial myofibroblasts (ISEMF) and intestinal epithelial cells. Wild-type and TnC(-/-) mice were treated with dextran sodium sulfate (DSS) to induce colitis.
  
  
  RESULTS
  DSS-induced colitis in mice markedly increased TnC in the damaged mucosal areas and up-regulated mRNA for TnC, pro-inflammatory cytokines and growth factors (PDGF-B and TGF-β1). In addition, 2,4,6-trinitrobenzene sulfonic acid-induced colitis and SAMP1/Yit mice, a model of spontaneous Crohn's disease, also exhibited increased mucosal TnC in colon and ilea respectively. PDGF receptor-α (PDGFRα) positive ISEMF were the primary TnC-producing cells in colon tissues. Accordingly, ISEMF collected from the rat colon constitutively expressed both TnC and PDGFRα. PDGF-BB and TGF-β1 up-regulated both TnC mRNA and protein levels in ISEMF. Knock-down of TnC gene increased susceptibility to DSS-induced colitis, compared with TnC(+/+) littermates. TnC(-/-) mice showed marked abrasion of intestinal mucosal barrier and increased inflammatory scores. Moreover, TnC accelerated both trans-well migration and wound healing in epithelial cells.
  
  
  CONCLUSIONS
  The pharmacological profiles of PDGF-BB and TGF-β in colitis tissues and ISEMF suggest that increased TnC production during inflammation contributed to epithelial cell migration, remodelling and protection of intestinal barriers.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: M S
authors.initials: MS
authors.lastname: Islam
authors.forename: M
authors.initials: M
authors.lastname: Kusakabe
authors.forename: K
authors.initials: K
authors.lastname: Horiguchi
authors.forename: S
authors.initials: S
authors.lastname: Iino
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Iwanaga
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: H
authors.initials: H
authors.lastname: Ozaki
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000897:Anti-Ulcer Agents; D015153:Blotting, Western; D002465:Cell Movement; D003092:Colitis / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007413:Intestinal Mucosa / Q000187:drug effects*; D007763:Lac Operon; D008297:Male; D051379:Mice; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D019063:Tenascin / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000199:Actins; D000897:Anti-Ulcer Agents; D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D012313:RNA; D020796:Receptor, Platelet-Derived Growth Factor alpha; D019063:Tenascin; D016212:Transforming Growth Factor beta; C498862:Acta2 protein, rat
keywords: ISEMF; PDGF; TGF-β; epithelial cell; intestinal inflammation; tenascin-C