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system, gut microbiota alteration, and epithelial dynamics in the colon contribute to the pathogenesis of inflammatory bowel disease (IBD). However, the role of epithelial dynamics, particularly epithelial regeneration, remains incompletely understood. CADM1 encodes an immunoglobulin-superfamily cell adhesion molecule involved in epithelial adhesion, immune cell interactions, and tumor suppression in colon and various cancers. Here, we investigated the role of CADM1 in IBD using a murine model of colitis induced by dextran sulfate sodium in both wild-type and conventional Cadm1-deficient (Cadm1\u2212\/\u2212) mice. Cadm1\u2212\/\u2212 mice exhibited more severe colitis than wild-type mice with increased mortality (64% vs. 10%) and delayed recovery. Cadm1\u2212\/\u2212 mice showed reduced numbers of Ki-67-positive cells in colonic crypts and delayed epithelial regeneration, whereas no significant differences were observed in epithelial apoptosis, intestinal permeability, or immune responses. Immunohistochemistry revealed that CADM1 expression was restricted to regenerative crypt cells in wild-type mice with nuclear accumulation of \u03b2-catenin and phospho-Akt. Furthermore, CADM1 overexpression in colon epithelial cells enhanced Tcf-transcriptional activity in a \u03b2-catenin-dependent manner. Immunohistochemistry of human IBD materials revealed that CADM1 expression also correlated with nuclear \u03b2-catenin accumulation in crypt epithelial cells. Collectively, CADM1 appears to promote colonic epithelial regeneration through the PI3K\/Akt\/\u03b2-catenin axis to protect against severe epithelial injury in IBD.<\/jats:p>","DOI":"10.3390\/ijms27093908","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Suppressor CADM1 Protects Against Colitis in Inflammatory Bowel Disease Through Enhancing Epithelial Regeneration"],"prefix":"10.3390","volume":"27","author":[{"given":"Yuki","family":"Hanaoka-Ikeda","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4372-6468","authenticated-orcid":false,"given":"Yutaka","family":"Kasai","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"},{"name":"Department of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Masuda","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"},{"name":"Department of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Ichihara","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"},{"name":"Department of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumiko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Division of Molecular and Developmental Biology, Institute of Medical Science, The University of Tokyo, Tokyo 113-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Shinozaki","sequence":"additional","affiliation":[{"name":"Department of Surgery, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"},{"name":"Department of Diagnostic Pathology, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"},{"name":"Department of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","first-page":"e065181","article-title":"Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: A systematic analysis based on the global burden of disease study 2019","volume":"13","author":"Wang","year":"2023","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: A therapeutic target?","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat. 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