{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:26:02Z","timestamp":1788279962464,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T00:00:00Z","timestamp":1706918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the MUC1 promoter, retinoic-acid-responsive elements in the MUC4 promoter, and butyrate-responsive elements in the MUC5B promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC.<\/jats:p>","DOI":"10.3390\/ijms25031858","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T05:22:44Z","timestamp":1707110564000},"page":"1858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing"],"prefix":"10.3390","volume":"25","author":[{"given":"Giuseppe","family":"Leoncini","sequence":"first","affiliation":[{"name":"First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0698-3872","authenticated-orcid":false,"given":"Luigi","family":"Cari","sequence":"additional","affiliation":[{"name":"Pharmacology Division, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5639-4243","authenticated-orcid":false,"given":"Simona","family":"Ronchetti","sequence":"additional","affiliation":[{"name":"Pharmacology Division, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-1019","authenticated-orcid":false,"given":"Francesco","family":"Donato","sequence":"additional","affiliation":[{"name":"Unit of Hygiene, Epidemiology and Public Health, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Caruso","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Pathology and Laboratory Medicine, Desenzano del Garda Hospital, ASST del Garda, 25015 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Calaf\u00e0","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Pathology and Laboratory Medicine, Desenzano del Garda Hospital, ASST del Garda, 25015 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Villanacci","sequence":"additional","affiliation":[{"name":"Institute of Pathology, ASST Spedali Civili, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3748\/wjg.v20.i1.91","article-title":"Inflammatory bowel disease: Pathogenesis","volume":"20","author":"Zhang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Melhem, H., Regan-Komito, D., and Niess, J.H. (2021). Mucins Dynamics in Physiological and Pathological Conditions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413642"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s10620-016-4032-6","article-title":"Mucin-Microbiota Interaction During Postnatal Maturation of the Intestinal Ecosystem: Clinical Implications","volume":"61","author":"Rokhsefat","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_4","first-page":"671","article-title":"Genetic variants of mucins: Unexplored conundrum","volume":"38","author":"Kumar","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1096\/fj.07-9673rev","article-title":"Structure, evolution, and biology of the MUC4 mucin","volume":"22","author":"Chaturvedi","year":"2008","journal-title":"FASEB J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jtos.2021.03.003","article-title":"Membrane-associated mucins of the human ocular surface in health and disease","volume":"21","author":"Fini","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"D1192","DOI":"10.2741\/Moniaux","article-title":"Structural organization and classification of the human mucin genes","volume":"6","author":"Moniaux","year":"2001","journal-title":"Front. Biosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cis.2017.12.005","article-title":"Gel-forming mucin interactome drives mucus viscoelasticity","volume":"252","author":"Demouveaux","year":"2018","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20563","DOI":"10.1016\/S0021-9258(20)80762-5","article-title":"Molecular cloning, sequence, and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC7)","volume":"268","author":"Bobek","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1016\/j.yexcr.2011.09.006","article-title":"Intestinal development and differentiation","volume":"317","author":"Noah","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1136\/gutjnl-2018-317571","article-title":"Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis","volume":"68","author":"Jabbar","year":"2019","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.cell.2015.10.072","article-title":"Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis","volume":"163","author":"Nowarski","year":"2015","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1038\/s41598-023-29649-y","article-title":"Intestinal epithelial barrier integrity investigated by label-free techniques in ulcerative colitis patients","volume":"13","author":"Quansah","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s12276-023-00960-y","article-title":"Intestinal mucus components and secretion mechanisms: What we do and do not know","volume":"55","author":"Song","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Myerscough, N., Warren, B., Gough, M., and Corfield, A. (1995). Expression of mucin genes in ulcerative colitis. Biochem. Soc. Trans., 23.","DOI":"10.1042\/bst023536s"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.tibs.2009.10.003","article-title":"Mucin-interacting proteins: From function to therapeutics","volume":"35","author":"Senapati","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/MCG.0b013e3182688e73","article-title":"Mucin function in inflammatory bowel disease: An update","volume":"47","author":"Boltin","year":"2013","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/00054725-199902000-00004","article-title":"Abnormalities in mucin gene expression in Crohn\u2019s disease","volume":"5","author":"Buisine","year":"1999","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1369\/jhc.5A6904.2006","article-title":"Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis","volume":"54","author":"Longman","year":"2006","journal-title":"J. Histochem. Cytochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1606910","article-title":"Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis","volume":"376","author":"Sandborn","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cgh.2019.02.044","article-title":"Comparative Risk of Serious Infections With Biologic and\/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis","volume":"18","author":"Singh","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1038\/s41375-022-01636-8","article-title":"Predictors of clonal evolution and myeloid neoplasia following immunosuppressive therapy in severe aplastic anemia","volume":"36","author":"Groarke","year":"2022","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jcmgh.2021.08.010","article-title":"Chronic Inflammation in Ulcerative Colitis Causes Long-Term Changes in Goblet Cell Function","volume":"13","author":"Singh","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"848344","DOI":"10.3389\/fmed.2022.848344","article-title":"The Role and Function of Mucins and Its Relationship to Inflammatory Bowel Disease","volume":"9","author":"Kang","year":"2022","journal-title":"Front. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.15403\/jgld-250","article-title":"Elevated Colonic Mucin Expression Correlates with Extended Time to Surgery for Ulcerative Colitis Patients","volume":"28","author":"Eshelman","year":"2019","journal-title":"J. Gastrointestin. Liver Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1042\/BCJ20170348","article-title":"Depletion of MUC5B mucin in gastrointestinal cancer cells alters their tumorigenic properties: Implication of the Wnt\/\u03b2-catenin pathway","volume":"474","author":"Lahdaoui","year":"2017","journal-title":"Biochem. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s00109-006-0100-2","article-title":"Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease","volume":"84","author":"Moehle","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.dld.2013.06.010","article-title":"Definition and evaluation of mucosal healing in clinical practice","volume":"45","author":"Mazzuoli","year":"2013","journal-title":"Dig. Liver Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1053\/j.gastro.2020.12.031","article-title":"STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD","volume":"160","author":"Turner","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.dld.2019.11.005","article-title":"Histopathology of inflammatory bowel disease\u2014Position statement of the Pathologists of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and Italian Group of Gastrointestinal Pathologists (GIPAD-SIAPEC)","volume":"52","author":"Villanacci","year":"2020","journal-title":"Dig. Liver Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6839","DOI":"10.1038\/s41598-017-07338-x","article-title":"Usefulness of Different Pathological Scores to Assess Healing of the Mucosa in Inflammatory Bowel Diseases: A Real Life Study","volume":"7","author":"Villanacci","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6143","DOI":"10.1038\/sj.onc.1208756","article-title":"Synergistic induction of the MUC4 mucin gene by interferon-gamma and retinoic acid in human pancreatic tumour cells involves a reprogramming of signalling pathways","volume":"24","author":"Andrianifahanana","year":"2005","journal-title":"Oncogene"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/ecco-jcc\/jjv089","article-title":"Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease","volume":"9","author":"Conway","year":"2015","journal-title":"J. Crohns. Colitis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1476-4598-11-24","article-title":"Nicotine, IFN-\u03b3 and retinoic acid mediated induction of MUC4 in pancreatic cancer requires E2F1 and STAT-1 transcription factors and utilize different signaling cascades","volume":"11","author":"Kunigal","year":"2012","journal-title":"Mol. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/bs.apha.2015.04.006","article-title":"Role of Retinoic Acid-Metabolizing Cytochrome P450s, CYP26, in Inflammation and Cancer","volume":"74","author":"Stevison","year":"2015","journal-title":"Adv. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mam.2011.11.001","article-title":"Vitamin A and immune regulation: Role of retinoic acid in gut-associated dendritic cell education, immune protection and tolerance","volume":"33","author":"Cassani","year":"2012","journal-title":"Mol. Aspects Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.devbrainres.2005.08.005","article-title":"Butyrate, a gut-derived environmental signal, regulates tyrosine hydroxylase gene expression via a novel promoter element","volume":"160","author":"Patel","year":"2005","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/jcb.22429","article-title":"A bipartite butyrate-responsive element in the human calretinin (CALB2) promoter acts as a repressor in colon carcinoma cells but not in mesothelioma cells","volume":"109","author":"Henzi","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"343","DOI":"10.4162\/nrp.2015.9.4.343","article-title":"Butyrate modulates bacterial adherence on LS174T human colorectal cells by stimulating mucin secretion and MAPK signaling pathway","volume":"9","author":"Jung","year":"2015","journal-title":"Nutr. Res. Pract."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1136\/gut.36.1.93","article-title":"Colonic mucin synthesis is increased by sodium butyrate","volume":"36","author":"Finnie","year":"1995","journal-title":"Gut"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"G1168","DOI":"10.1152\/ajpgi.00219.2004","article-title":"Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose","volume":"287","author":"Gaudier","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.3945\/jn.109.104638","article-title":"Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers","volume":"139","author":"Peng","year":"2009","journal-title":"J. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/ibd.21177","article-title":"Enhanced translocation of bacteria across metabolically stressed epithelia is reduced by butyrate","volume":"16","author":"Lewis","year":"2010","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1111\/den.13863","article-title":"The endoscopic diagnosis of mucosal healing and deep remission in inflammatory bowel disease","volume":"33","author":"Moriichi","year":"2021","journal-title":"Dig. Endosc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41586-019-1237-9","article-title":"Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases","volume":"569","author":"Arze","year":"2019","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.dib.2017.07.057","article-title":"Prediction of transcription factor bindings sites affected by SNPs located at the osteopontin promoter","volume":"14","author":"Coombes","year":"2017","journal-title":"Data Br."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:54:22Z","timestamp":1760104462000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,3]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031858"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031858","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,3]]}}}