RRC ID 44690
Author Islam MS, Kusakabe M, Horiguchi K, Iino S, Nakamura T, Iwanaga K, Hashimoto H, Matsumoto S, Murata T, Hori M, Ozaki H.
Title PDGF and TGF-β promote tenascin-C expression in subepithelial myofibroblasts and contribute to intestinal mucosal protection in mice.
Journal Br J Pharmacol
Abstract BACKGROUND AND PURPOSE: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.
EXPERIMENTAL APPROACH: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.
KEY 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 AND IMPLICATIONS: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.
Volume 171(2)
Pages 375-88
Published 2014-1-1
DOI 10.1111/bph.12452
PMID 24116743
PMC PMC3904258
MeSH Actins / biosynthesis Actins / genetics Animals Anti-Ulcer Agents* Blotting, Western Cell Movement Colitis / metabolism Colitis / pathology Cytokines / metabolism Epithelial Cells / drug effects Epithelial Cells / metabolism Fluorescent Antibody Technique Intestinal Mucosa / drug effects* Lac Operon Male Mice Microscopy, Immunoelectron Molecular Sequence Data Myofibroblasts / drug effects Myofibroblasts / metabolism* Platelet-Derived Growth Factor / pharmacology* RNA / biosynthesis RNA / genetics Rats Rats, Sprague-Dawley Receptor, Platelet-Derived Growth Factor alpha / metabolism Tenascin / biosynthesis* Transforming Growth Factor beta / pharmacology* Wound Healing / drug effects
IF 7.73
Times Cited 23
Human and Animal Cells IEC 6(RCB0993)