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.

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.

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.

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.