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Project

Study of the mechanisms involved in MUC1/MUC13-induced intestinal barrier disruption during inflammatory bowel diseases: a translational approach.

Next to inflammation, intestinal barrier dysfunction is an important mechanism related to the pathogenesis of inflammatory bowel diseases (IBD). The mechanisms underlying an altered barrier function in IBD, in particular the role of mucins (MUC), remain largely unexplored. Our own pilot data show an increased expression of MUC1 and MUC13 in inflamed biopsies from IBD patients. These MUCs are thought to disturb cell polarity complexes and tight junctions eventually resulting in an intestinal barrier dysfunction. Nevertheless, the exact role of MUC1 and MUC13 in the epithelial response to acute or chronic inflammation remains poorly understood. Therefore, we will first unravel the mechanisms by which these mucins affect intestinal barrier permeability upon inflammation using 3D-mini guts (organoids), the Ussing chamber technique and IBD mouse models. In parallel, the obtained results will be translated to IBD patients in order to identify MUC1 and MUC13 as novel targets for therapy and/or biomarkers, as still a large number of patients fail to respond or obtain full remission with the current therapies. To do so, the mechanisms of action of MUC1 and MUC13 affecting barrier integrity will be verified. Thereafter, the expression levels of MUC1, MUC13 and their barrier mediators will be investigated by single-cell RNA sequencing and subsequently correlated to the mucosal permeability and clinical outcome parameters.
Date:1 Nov 2020 →  Today
Keywords:INFLAMMATORY BOWEL DISEASE, MOUSE MODELS
Disciplines:Gastro-enterology, Inflammation, Membrane structure and transport, Transcription and translation, Cell physiology