{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:42Z","timestamp":1753869402099,"version":"3.41.2"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aryl hydrocarbon receptor (AhR) is a ligand\u2010dependent transcription factor. We previously reported spontaneous ileocecal tumorigenesis in AhR\u2010deficient mice after the age of 10 weeks, which originated in the confined area between ileum and cecum. This study aimed to investigate the underlying mechanism that causes tumor development at this particular location. To observe mucosal architecture in detail, tissues of ileocecal region were stained with methylene blue. Gene expression profile in the ileocecal tissue was compared with cecum. Immunohistochemical analysis was performed with ileocecal tissues using antibodies against ileum\u2010specific Reg3\u03b2 or cecum\u2010specific Pitx2. In <jats:italic>AhR<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice and <jats:italic>AhR<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice, that do not develop lesions, methylene blue staining revealed the gradually changing shape and arrangement of villi from ileum to cecum. It was also observed in AhR\u2010deficient mice before developing lesions. Microarray\u2010based analysis revealed abundant antimicrobial genes, such as Reg3, in the ileocecal tissue while FGFR2 and Pitx2 were specific to cecum. Immunohistochemical analysis of AhR\u2010deficient mice indicated that lesions originated from the ileocecal junction, a boundary area between different epithelial types. Site\u2010specific gene expression analysis revealed higher expression of IL\u20101\u03b2 at the ileocecal junction compared with the ileum or cecum of 9\u201311\u2010week\u2010old AhR\u2010deficient mice. These findings indicate that AhR plays a vital function in the ileocecal junction. Regulating AhR activity can potentially manage the stability of ileocecal tissue possessing cancer\u2010prone characteristics. This investigation contributes to understanding homeostasis in different epithelial transitional tissues, frequently associated with pathological states.<\/jats:p>","DOI":"10.1002\/jbt.23736","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T04:54:10Z","timestamp":1716267250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor formation at ileocecal junction associated with interleukin\u20101\u03b2 upregulation in aryl hydrocarbon receptor\u2010deficient mouse"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3993-5176","authenticated-orcid":false,"given":"Togo","family":"Ikuta","sequence":"first","affiliation":[{"name":"Department of Cancer Prevention Research Institute for Clinical Oncology, Saitama Cancer Center Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Pathology Saitama Cancer Center Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2773"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90958-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1271"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2011.07.011"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3846"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.04.014"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2016.03.012"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.13.1742"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.630938"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600822"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2013.11.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1191536"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15207"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00551"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp0600438"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230309746"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095058"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205633"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2882"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21583"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1966"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902132106"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgt083"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.10.005"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50146"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(05)00283-1"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.1997.1490345.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.12.028"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.05.002"},{"volume-title":"Morson and Dawson's Gastrointestinal Pathology","year":"2013","author":"Petras R. 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