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

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.

The novel role of glucocorticoid-induced leucine zipper as a marker of mucosal healing in inflammatory bowel diseases.

Glucocorticoid-induced leucin zipper (GILZ) mediates the effects of glucocorticoids in immune cells, but little is known about its role in both the gastro-intestinal (GI) mucosa and inflammatory bowel diseases (IBD) in humans. To investigate the GILZ protein expression profile in the GI tract, mucosal biopsies from 80 patients were retrospectively enrolled in this study and subdivided into three groups: 1) patients without clinical-endoscopic and histological evidence of IBD; 2) IBD patients; 3) patients with chronic atrophic gastritis (CAG) and Barrett esophagus (BE), both characterized by intestinal metaplasia (IM). GILZ expression was assessed by immunohistochemical and immunofluorescence methods. Our results showed that GILZ protein was strongly expressed in the secretory cells in healthy mucosa. GILZ expression was reduced in goblet cells in active disease, whereas it was restored in quiescent diseases. Conversely, entero-endocrine cells were not involved in such inflammation-driven dynamics, as GILZ expression remained detectable in active disease. Moreover, GILZ was expressed in IM, but was limited to CAG, and was not detected in BE. In summary, GILZ acts as a secretory protein in the GI mucosa in healthy, hyperplastic and metaplastic conditions. Its secretion by goblet cells is mostly affected by neutrophils mucosal infiltration and seems to be directly related to active mucosal inflammation in IBD. Overall, our findings suggest that GILZ is a suitable molecule to be considered as a histological marker of mucosal healing.