Abstract
Abstract The aim of this study is to determine the role of membrane mucin MUC17 in Crohn’s disease (CD). The incidence of CD is increasing in Western countries. However, the epithelial defects that cause disease are unclear. CD is characterized by the disruption of intestinal barriers leading to detrimental bacterial challenges that result in chronic intestinal inflammation. Our recent studies show that enterocytes are coated by the membrane mucin MUC17 that creates a glycocalyx barrier that protects enterocytes against luminal bacteria (Layunta et al. 2021 Accepted). Despite recent advances in defining intestinal barriers, the role of MUC17 and glycocalyx in CD remains unknown. In order to determine the role of MUC17 and glycocalyx in CD, we studied MUC17 and glycocalyx in ileum biopsies from CD (n=10) and non-CD (n=29) patients collected at Sahlgrenska University Hospital (Gothenburg). Our preliminary data show that MUC17 is downregulated in CD. In mouse ileum, MUC17 forms the glycocalyx barrier. Then, we asked if decrement of MUC17 levels could affect glycocalyx barrier function in CD. To address this question we designed a glycocalyx permeability assay in which we can measure the barrier function of MUC17 in glycocalyx by incubating patient biopsies with live GFP-expression E.coli (GFP+ E.Coli) and exogenous molecules such as fluorescent dextran. Our results showed that the glycocalyx in ileum of CD patients was more penetrable to GFP+ E.Coli and dextran compared to non-CD patients. In summary, we propose that changes in MUC17 levels in the glycocalyx contributes to disruption of epithelial barrier function during CD. In addition, our novel glycocalyx permeability assay can be used to diagnose CD, and to evaluate treatment response in patients.
Published Version
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