A165 FCGBP IN THE COLON IS SPATIALLY DEPENDENT ON MUC2 EXPRESSION AND IS DEGRADED IN DEXTRAN SULFATE SODIUM-INDUCED COLITIS

Abstract Background The colonic mucus bilayer is an integral innate host defense mechanism that provides a physical barrier separating the lumen and its contents from underlying epithelium. This essential produced by specialized secretory goblet cells of which Muc2 mucin primary product. IgG-Fc-binding protein (Fcgbp) second most abundant cells, has suggested function crosslinking with to stabilize structural integrity mucus. FCGBP observed decrease preceding onset inflammation in ulcerative colitis patients, leading spatially distinct weakening contribute pathogenesis disease. Purpose Fcgbp altered regionally gut plays role dextran sulfate sodium (DSS)-induced colitis. specific aims are: To characterize spatial expression basally quantify alterations response DSS-induced at restitution disease Method mRNA Muc2+/+ Muc2-/- C57BL/6 littermates were analyzed RT-qPCR Western blotting, respectively. Mucin granules isolated proteome quantified liquid chromatography tandem mass spectrometry (LC-MS/MS). Colitis was induced mice 3.5% (w/v) DSS tap water for five days, whereas given 1.5% three ad libitum. Mice regular remainder experiment allow inflammation. Disease activity index (DAI) scored based on weight loss. sacrificed various time points up 10 colons excised sectioned histopathology analysis. Result(s) LC-MS/MS run under reducing non-reducing conditions confirmed proteins non-covalently bound each other. highly expressed mid colon, regulation unaffected littermates. In mice, transcription rapidly increased all regions colon highest colon. contrast, distal peaked during activity. Interestingly, abrogated even restitution. decreased but returned normal levels following removal DSS. Image Conclusion(s) study demonstrates DSS, degraded remained low disappearance littermates, despite restoration, suggests remains structurally functionally impaired Supported CIHR Disclosure Interest None Declared