Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing
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Published:2024-02-03
Issue:3
Volume:25
Page:1858
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Leoncini Giuseppe1, Cari Luigi2ORCID, Ronchetti Simona2ORCID, Donato Francesco3ORCID, Caruso Laura4, Calafà Cristina4, Villanacci Vincenzo5
Affiliation:
1. First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy 2. Pharmacology Division, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy 3. Unit of Hygiene, Epidemiology and Public Health, University of Brescia, 25123 Brescia, Italy 4. Pathology Unit, Department of Pathology and Laboratory Medicine, Desenzano del Garda Hospital, ASST del Garda, 25015 Brescia, Italy 5. Institute of Pathology, ASST Spedali Civili, 25123 Brescia, Italy
Abstract
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.
Funder
the Italian Group for the Study of Inflammatory Bowel Disease
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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