{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:16:53Z","timestamp":1787894213120,"version":"build-2784847793"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007830","name":"Kitasato University","doi-asserted-by":"crossref","award":["2025-47"],"award-info":[{"award-number":["2025-47"]}],"id":[{"id":"10.13039\/501100007830","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007830","name":"Kitasato University","doi-asserted-by":"crossref","award":["2026-15"],"award-info":[{"award-number":["2026-15"]}],"id":[{"id":"10.13039\/501100007830","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007830","name":"Kitasato University","doi-asserted-by":"crossref","award":["2023-4023"],"award-info":[{"award-number":["2023-4023"]}],"id":[{"id":"10.13039\/501100007830","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2025-47"],"award-info":[{"award-number":["2025-47"]}],"id":[{"id":"https:\/\/ror.org\/00f2txz25","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2026-15"],"award-info":[{"award-number":["2026-15"]}],"id":[{"id":"https:\/\/ror.org\/00f2txz25","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2023-4023"],"award-info":[{"award-number":["2023-4023"]}],"id":[{"id":"https:\/\/ror.org\/00f2txz25","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intestinal barrier dysfunction and mucus layer abnormalities are central features of inflammatory bowel disease, yet the epithelial mechanisms regulating goblet cell function remain incompletely understood. The TWEAK\/Fn14 pathway is involved in intestinal inflammation, but its role in small intestinal epithelial responses, particularly in goblet cells, has not been fully clarified. In this study, we investigated TWEAK\/Fn14 signaling using mouse small intestinal epithelial organoids. Fn14 was expressed in MUC2-positive cells in intestinal tissue, with staining preferentially observed toward the mucin-facing region. Fn14 staining was also observed in small intestinal epithelial organoids. TWEAK stimulation increased Tnf mRNA expression by approximately 1.56-fold and reduced Muc2 mRNA expression to approximately 66% of control, without markedly affecting epithelial proliferation or stem cell markers. TWEAK did not significantly alter the PAS-positive mucin area or AB-PAS-defined mucin composition, whereas PGM34 staining showed a non-significant tendency to increase. TNF treatment reproduced some of the TWEAK-associated changes, including reduced Muc2 mRNA expression and alterations in mucin-associated parameters, suggesting that TNF may contribute to some of the epithelial responses associated with TWEAK treatment. Treatment with an anti-TNF neutralizing antibody modified several TWEAK-associated responses, including changes in epithelial-associated gene expression and mucin-associated staining parameters. These findings suggest that TWEAK treatment is associated with goblet cell-related mucin responses in mouse small intestinal epithelial organoids, with possible involvement of TNF signaling.<\/jats:p>","DOI":"10.3390\/cells15171541","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:04:32Z","timestamp":1787756672000},"page":"1541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TWEAK\/Fn14 Signaling Modulates Goblet Cell-Associated Mucin Responses in Mouse Small Intestinal Epithelial Organoids"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7722-5623","authenticated-orcid":false,"given":"Shun","family":"Tamaki","sequence":"first","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Biochemistry, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Clinical Research Advancement Section, National Institute of Global Health and Medicine, Japan Institute for Health Security (JIHS), Shinjuku 162-8655, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakura","family":"Arikawa","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Clinical Research 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Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Gastroenterology, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Gastroenterology, School of Medicine, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taizo","family":"Tsujimoto","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Gastroenterology, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Gastroenterology, School of Medicine, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-2516","authenticated-orcid":false,"given":"Fumitaka","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Health Administration, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoki","family":"Imai","sequence":"additional","affiliation":[{"name":"Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3272-1470","authenticated-orcid":false,"given":"Yoshifumi","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Clinical Chemistry Laboratory, Department of Medical Laboratory Sciences, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shokichi","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Nephrology, School of Medicine, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohito","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Clinical Chemistry Laboratory, Department of Medical Laboratory Sciences, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Biochemistry, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3242-1967","authenticated-orcid":false,"given":"Rei","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Department of Biochemistry, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"},{"name":"Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 Inflammatory Bowel Disease Collaborators (2020). 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