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Core 1- and core 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice

Core 1- and core 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We foun...

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Detalles Bibliográficos
Autores principales: Bergstrom, Kirk, Fu, Jianxin, Johansson, Malin EV, Liu, Xiaowei, Gao, Nan, Wu, Qian, Song, Jianhua, McDaniel, J Michael, McGee, Samuel, Chen, Weichang, Braun, Jonathan, Hansson, Gunnar C, Xia, Lijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097036/
https://www.ncbi.nlm.nih.gov/pubmed/27143302
http://dx.doi.org/10.1038/mi.2016.45
Descripción
Sumario:Core 1- and core 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O-glycans, was detected throughout the colon, whereas C3GnT, which controls core 3 O-glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1-derived O-glycans (IEC C1galt1(−/−)) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1- and core 3-derived O-glycans (DKO) developed spontaneous colitis in both distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1(−/−) mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than WT mucins. This study indicates that core 1- and 3-derived O-glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients.