論文 - 詳細
| RRC ID | 44690 |
|---|---|
| 著者 | Islam MS, Kusakabe M, Horiguchi K, Iino S, Nakamura T, Iwanaga K, Hashimoto H, Matsumoto S, Murata T, Hori M, Ozaki H. |
| タイトル | PDGF and TGF-β promote tenascin-C expression in subepithelial myofibroblasts and contribute to intestinal mucosal protection in mice. |
| ジャーナル | 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. |
| 巻・号 | 171(2) |
| ページ | 375-88 |
| 公開日 | 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 |
| 引用数 | 23 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| リソース情報 | |
| ヒト・動物細胞 | IEC 6(RCB0993) |