Transglutaminase 2 is dispensable but required for the survival of mice in dextran sulfate sodium-induced colitis.
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.
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea.|Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, South Korea.
Eui Man
0000-0003-0692-2033
EM
Jeong
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea.
Young Hoon
YH
Son
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea.
Yewon
Y
Choi
Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea.
Jin-Hee
JH
Kim
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea.
Jin-Haeng
JH
Lee
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea.|Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, South Korea.
Sung-Yup
SY
Cho
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea.|Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, South Korea.
In-Gyu
IG
Kim
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D016264:Dextran Sulfate; D004789:Enzyme Activation; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D058504:Th17 Cells / Q000378:metabolism / Q000473:pathology; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
D016264:Dextran Sulfate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins