title: Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis.
abstract: OBJECTIVE
  This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction.
  
  
  METHODS
  Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay.
  
  
  RESULTS
  The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis.
  
  
  CONCLUSIONS
  There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Bosi
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Gastroenterology and Hepatology, The First People's Hospital of Huainan, Huainan, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Youke
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Fangyu
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D057167:Claudins / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D003106:Colon / Q000276:immunology / Q000503:physiopathology; D016264:Dextran Sulfate; D007413:Intestinal Mucosa / Q000503:physiopathology*; D007792:Lactulose / Q000378:metabolism; D008353:Mannitol / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000276:immunology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D057167:Claudins; D037601:Mannose-Binding Lectin; D008353:Mannitol; D007792:Lactulose; D013395:Sucrose; D016264:Dextran Sulfate; C026285:trichlorosucrose
keywords: Apoptosis; Claudin; Colitis, ulcerative; Intestinal permeability; Mannan-binding lectin-associated serine proteases 2