Alterations in the Composition of the Supramucosal Defense Barrier in Relation to Disease Severity of Ulcerative Colitis

Abstract

Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expression was upregulated in severe UC at the site of rupture of crypt abscesses. Reduction in MUC2 expression occurred in UC adjacent to ulceration. No alteration in MUC3 or MUC4 gene expression was detectable in UC compared with normal colorectal mucosa. No ectopic expression of MUC5AC, MUC5B, or MUC6 was identified in UC. Ectopic TFF1 expression was identified in tissues eliciting histological features of severe disease. Decreased TFF3 localization was demonstrated in UC tissues, but no TFF2 expression was detected in any colorectal specimens. Subtle alterations in composition of the supramucosal defense barrier exist in UC and vary in relation to clinical severity of disease. There is upregulation in mucin MUC1 at crypt abscesses and neo-expression of TFF1 trefoil peptide in severe disease.

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“…1J). Our histology results are consistent with the recent publication by Longman et al (16) reporting increased MUC1 mRNA expression in crypts and goblet cells in colon samples from a large number of patients with severe UC.…”

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“…Colonic TFF3 expression was found reduced in trinitro-benzene-sulfonic acid-induced rat colitis (38). In UC patients, reduced TFF3 expression was more pronounced with increasing disease severity (39). We found TFF3 mRNA expression significantly decreased in MFG-E8 knockdown HT-29 IECs, which suggests a potential molecular basis responsible for impaired wound healing.…”

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