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Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.

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.

SUBMITTER: Leoncini G

PROVIDER: S-EPMC10855303 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.

Leoncini Giuseppe G Cari Luigi L Ronchetti Simona S Donato Francesco F Caruso Laura L Calafà Cristina C Villanacci Vincenzo V

International journal of molecular sciences 20240203 3

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 immunohistoch ...[more]

PMID: 38339134

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Project description:BackgroundClinical remission is the recommended treatment target in ulcerative colitis. The predictors and outcomes of achieving histologic remission within a treat-to-target paradigm are not well established.AimTo evaluate the predictors and outcomes of achieving histologic remission in patients with ulcerative colitis treated-to-target of endoscopic healing (modified Mayo endoscopy score 0 or 1).MethodsWe conducted a retrospective cohort study in adults with active ulcerative colitis (modified Mayo endoscopy score 2 or 3), whose treatment was iteratively optimised to achieve endoscopic healing. We identified predictors of achieving histologic remission, and outcomes (risk of symptomatic relapse, and ulcerative colitis-related hospitalisation and/or surgery) of achieving histologic remission vs persistent histologic activity, using Cox proportional hazard analysis.ResultsOf the 411 patients with clinically active ulcerative colitis, 270 achieved endoscopic healing. Of the 270 patients, 55% simultaneously achieved histologic remission. Depth of endoscopic healing at final endoscopic assessment was the only independent determinant of histologic remission (modified Mayo endoscopy score 0 vs 1: odds ratio, 0.31 [95% confidence intervals, 0.18-0.52]). Over 28 months, achieving histologic remission was associated with a lower risk of clinical relapse (1-year cumulative risk: 18.7% vs 29.5%; adjusted hazard ratio, 0.56 [0.37-0.85]), and lower risk of hospitalisation (hazard ratio, 0.44 [0.20-0.94]). The incremental benefit of achieving histologic remission was observed only in patients achieving Mayo endoscopy score 1, but not Mayo endoscopy score 0.ConclusionsIn patients with active ulcerative colitis treated-to-target of endoscopic healing, 55% simultaneously achieved histologic remission. Histologic remission, particularly in patients achieving modified Mayo endoscopy score 1, was associated with favourable outcomes. Treating to a target of histologic remission over endoscopic healing requires prospective evaluation.

Dataset Information

Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.

Publications

Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.

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