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Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation.

Journal article
Authors Jessica Holmén Larsson
Hasse Karlsson
Jessica Gråberg Crespo
Malin E V Johansson
Lisbeth Eklund
Henrik Sjövall
Gunnar C. Hansson
Published in Inflammatory bowel diseases
ISSN 1536-4844
Publication year 2011
Published at Institute of Medicine, Department of Internal Medicine
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Links dx.doi.org/10.1002/ibd.21625
Subject categories Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Abstract

BACKGROUND: The MUC2 mucin organizes the two mucus layers in the colon. This mucin carries a large number of O-glycans that are assumed to be attachment sites for the commensal flora found in the outer mucus layer. METHODS: Single biopsies from the sigmoid colon of controls (25) and patients with inactive (13) or active (15) ulcerative colitis (UC) were collected during routine colonoscopy. The insoluble MUC2 mucin was prepared and separated by gel electrophoresis, its relative amount estimated, its O-glycans released, and glycans analyzed by novel sensitive glycomics chromatography / mass spectrometry providing information on glycan structures and relative abundances. The glycosylation pattern was related to the degree of mucosal inflammation and clinical severity of the disease. RESULTS: The relative abundance of MUC2 showed high individual variability. Two major glycan profiles were found; a normal pattern in the control and inactive UC patients and an aberrant profile in patients with active colitis with an increase in a subset of the smaller glycans and a decrease of several complex glycans. The magnitude of this phenomenon was significantly related to both the degree of inflammation in the biopsies and also to some extent the severity of disease course. The aberrant profile was further shown to be reversible upon remission. CONCLUSIONS: In the majority of the active UC patients MUC2 mucin has an altered glycan profile as compared to inactive UC and control patients. Patients with strong alterations in the glycan pattern tended to have a more severe disease course. (Inflamm Bowel Dis 2011).

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