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ABSTRACT Background & Aims Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) where a defect in the colonic epithelial barrier elicits a chronic and unresolved inflammatory response against luminal microbiota. Mucins are heavily glycosylated proteins secreted by goblet cells that form gelatinous layers to protect the colonic epithelium. Whereas the role of the major colonic mucin, MUC2, is established in UC, few reports have analyzed MUC5B in this disease. In this study, we investigated MUC5B expression in colonic tissues and organoid cultures from UC patients and non-IBD controls. Methods MUC5B transcripts were analyzed in colonic regions from UC patients and controls using RT-qPCR. MUC5B protein levels in colonic tissues were analyzed and quantified by immunohistochemistry. Patient-derived epithelial organoids were stained for MUC5B, E-cadherin and F-actin. Organoids were treated with interleukin 1 beta (IL-1β) and MUC5B transcripts were analyzed by RT-qPCR. MUC5B proteins were assessed in IL-1β-treated organoids by immunofluorescent microscopy. Results MUC5B transcripts and proteins were expressed in the healthy colon and their levels were decreased in UC tissues. MUC5B proteins were reduced in organoids derived from UC tissues. IL-1β treatment of control organoids stimulated expression of acidic mucins, MUC5B transcripts and MUC5B proteins. MUC5B transcripts were not induced by IL-1β in UC-derived organoids. Conclusions MUC5B levels are reduced in UC colons and its expression is induced by the IL-1β pro-inflammatory cytokine. These results suggest that MUC5B contributes to the protective colonic mucin layer and that this function is likely compromised in UC.
Ding et al. (Fri,) studied this question.