Exp Mol Med.  2016 Nov;48(11):e267. 10.1038/emm.2016.95.

Transglutaminase 2 is dispensable but required for the survival of mice in dextran sulfate sodium-induced colitis

• Jeong EM
• Son YH
• Choi Y
• Kim JH
• Lee JH
• Cho SY
• Kim IG

• KMID: 2362291
• DOI: http://doi.org/10.1038/emm.2016.95

Abstract

Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that catalyzes crosslinking, polyamination or deamidation of glutamine residues in proteins. It has been reported that TG2 is involved in the pathogenesis of various inflammatory diseases including celiac disease, pulmonary fibrosis, cystic fibrosis, multiple sclerosis and sepsis. Recently, using a mouse model of bleomycin-induced lung fibrosis, we showed that TG2 is required to trigger inflammation via the induction of T helper type 17 (Th17) cell differentiation in response to tissue damage. However, the role of TG2 in inflammatory bowel disease (IBD), which is thought to be a Th17 cell-associated disease, has remained elusive. In this study, we investigated the role of TG2 in dextran sulfate sodium (DSS)-induced colitis, the most widely used mouse model for IBD. Age- and sex-matched wild-type and TG2(−/−) mice were fed 2% DSS for 7 days or 3.5% DSS for 5 days in drinking water. An in situ TG activity assay revealed that DSS treatment activates TG2 in various colon cell types, including columnar absorptive cells and goblet cells. DSS-treated TG2(−/−) mice showed lower interleukin (IL)-6, but higher IL-17A and RORγt (retinoic acid receptor-related orphan receptor-γt) expression levels in the colon tissues than that in the wild-type mice. Moreover, TG2(−/−) mice showed higher mortality than the wild-type mice because of DSS treatment. Nevertheless, we found no significant differences in changes of body weight, colon length, morphology, immune cell infiltration and in vivo intestinal permeability between DSS-treated wild-type and TG2(−/−) mice. These results indicate that TG2-mediated Th17 cell differentiation is not required for the pathogenesis of DSS-induced acute colitis.

MeSH Terms

Animals
Body Weight
Celiac Disease
Cell Differentiation
Child
Child, Orphaned
Colitis*
Colon
Cystic Fibrosis
Dextran Sulfate*
Dextrans*
Drinking Water
Fibrosis
Glutamine
Goblet Cells
Humans
Inflammation
Inflammatory Bowel Diseases
Interleukin-17
Interleukins
Lung
Mice*
Mortality
Multiple Sclerosis
Permeability
Pulmonary Fibrosis
Sepsis
Th17 Cells
Dextran Sulfate
Dextrans
Drinking Water
Glutamine
Interleukin-17
Interleukins