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.
- Author:
Bosi YUAN
1
;
Shuping ZHOU
;
Youke LU
;
Jiong LIU
;
Xinxin JIN
;
Haijun WAN
;
Fangyu WANG
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: Colitis, ulcerative; Claudin; Intestinal permeability; Apoptosis; Mannan-binding lectin-associated serine proteases 2
- MeSH: Animals; Apoptosis/*physiology; Claudins/*metabolism; Colitis/chemically induced/immunology/*physiopathology; Colon/immunology/physiopathology; Dextran Sulfate; Intestinal Mucosa/*physiopathology; Lactulose/metabolism; Mannitol/metabolism; Mannose-Binding Lectin/*immunology; Permeability; Rats; Rats, Sprague-Dawley; Sucrose/analogs & derivatives/metabolism; Up-Regulation
- From:Gut and Liver 2015;9(6):734-740
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: 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.
