KMID : 0620920190510100128
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Experimental & Molecular Medicine 2019 Volume.51 No. 10 p.128 ~ p.128
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Gadd45¥â promotes regeneration after injury through TGF¥â-dependent restitution in experimental colitis
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Hwang Jung-Hwan
Kim Tae-Hwan Kim Yong-Hoon Noh Jung-Ran Choi Dong-Hee Kim Kyoung-Shim Lee Eun-Young Kim Byoung-Chan Kim Myung-Hee Kim Ho Lee Tae-Geol Lee Jong-Soo Lee Chul-Ho
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Abstract
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Dysregulated immune responses and impaired function in intestinal epithelial cells contribute to the pathogenesis of inflammatory bowel disease (IBD). Growth arrest and DNA damage-inducible 45 beta (Gadd45¥â) has been implicated in the pathogenesis of various inflammatory symptoms. However, the role of Gadd45¥â in IBD is completely unknown. This study aimed to evaluate the role of Gadd45¥â in IBD. Gadd45¥â-KO mice exhibited drastically greater susceptibility to dextran sulfate sodium (DSS)-induced colitis and mortality than C57BL/6J mice. Bone marrow transplantation experiments revealed that Gadd45¥â functions predominantly in the intestinal epithelium and is critical during the recovery phase. Gadd45¥â regulates the TGF-¥â signaling pathway in colon tissue and epithelial cells by inhibiting Smurf-mediated degradation of TGF-¥â receptor type 1 via competitive binding to the N-terminal domain of Smad7. Furthermore, these results indicate that the Gadd45¥â-regulated TGF-¥â signaling pathway is involved in wound healing by enhancing epithelial restitution. These results expand the current understanding of the function of Gadd45¥â and its therapeutic potential in ulcerative colitis.
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KEYWORD
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Acute inflammation, Mechanisms of disease
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