title: Core 1- and 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice.
abstract: Core 1- and 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 3-derived O-glycans (DKO) developed spontaneous colitis in both the 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 wild-type 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.
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bergstrom
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.|Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: M E V
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: The Second Affiliated Hospital, Central South University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: N
authors.initials: N
authors.lastname: Gao
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: McDaniel
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: S
authors.initials: S
authors.lastname: McGee
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Braun
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: G C
authors.initials: GC
authors.lastname: Hansson
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.|Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, China.|Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xia
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D004195:Disease Models, Animal; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000276:immunology / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D059748:Proteolysis
chemical_list: D000900:Anti-Bacterial Agents; D011134:Polysaccharides; C515597:C1galt1 protein, mouse; D005700:Galactosyltransferases; D017351:N-Acetylglucosaminyltransferases; C117361:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3