TDAG51 deficiency attenuates dextran sulfate sodium-induced colitis in mice

• Published in: Scientific reports Vol. 12; no. 1; pp. 20619 - 13
• Main Authors: Jeon, Hyoeun, Amarasekara, Dulshara Sachini, Lee, Nari, Park, Hye-Won, Yu, Jiyeon, Rho, Jaerang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-11-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 631/250; 631/337; 692/4017; 692/4020; Animals; Body weight; Cell death; Colitis - chemically induced; Colon; Crohn's disease; Cytokines; Dextran; Dextran sulfate; Dextran Sulfate - toxicity; Disease; Etiology; Gastrointestinal tract; Humanities and Social Sciences; Inflammation Mediators; Inflammatory bowel disease; Inflammatory Bowel Diseases; Lethality; Lymphocytes T; Mice; multidisciplinary; Pathogenesis; Rodents; Science; Science (multidisciplinary); Sodium; Sulfates; Therapeutic targets; Ulcerative colitis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-24873-4

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a group of chronic inflammatory diseases of the gastrointestinal tract. Although the multifactorial etiology of IBD pathogenesis is relatively well documented, the regulatory factors that confer a risk of IBD pathogenesis remain less explored. In this study, we report that T-cell death-associated gene 51 (TDAG51/PHLDA1) is a novel regulator of the development of dextran sulfate sodium (DSS)-induced colitis in mice. TDAG51 expression was elevated in the colon tissues of DSS-induced experimental colitis mice. TDAG51 deficiency protected mice against acute DSS-induced lethality and body weight changes and disease severity. DSS-induced structural damage and mucus secretion in colon tissues were significantly reduced in TDAG51-deficient mice compared with wild-type mice. We observed similar results in a DSS-induced chronic colitis mouse model. Finally, we showed that the production of inflammatory mediators, including proinflammatory enzymes, molecules and cytokines, was decreased in DSS-treated TDAG51-deficient mice compared with DSS-treated wild-type mice. Thus, we demonstrated that TDAG51 deficiency plays a protective role against DSS-induced colitis by decreasing the production of inflammatory mediators in mice. These findings suggest that TDAG51 is a novel regulator of the development of DSS-induced colitis and is a potential therapeutic target for IBD.