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Dysregulated immune responses and impaired function in intestinal epithelial cells contribute to the pathogenesis ofinflammatory bowel disease (IBD). Growth arrest and DNA damage-inducible 45 beta (Gadd45β) has been implicatedin the pathogenesis of various inflammatory symptoms. However, the role of Gadd45β in IBD is completely unknown. This study aimed to evaluate the role of Gadd45β in IBD. Gadd45β-KO mice exhibited drastically greater susceptibilityto dextran sulfate sodium (DSS)-induced colitis and mortality than C57BL/6J mice. Bone marrow transplantationexperiments revealed that Gadd45β functions predominantly in the intestinal epithelium and is critical during therecovery phase. Gadd45β regulates the TGF-β signaling pathway in colon tissue and epithelial cells by inhibitingSmurf-mediated degradation of TGF-β receptor type 1 via competitive binding to the N-terminal domain of Smad7. Furthermore, these results indicate that the Gadd45β-regulated TGF-β signaling pathway is involved in wound healingby enhancing epithelial restitution. These results expand the current understanding of the function of Gadd45β and itstherapeutic potential in ulcerative colitis.
