Gut Liver.  2015 Nov;9(6):734-740. 10.5009/gnl14155.

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

Affiliations
  • 1Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. cat409@126.com
  • 2Department of Gastroenterology and Hepatology, The First People's Hospital of Huainan, Huainan, China.

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.

Keyword

Colitis, ulcerative; Claudin; Intestinal permeability; Apoptosis; Mannan-binding lectin-associated serine proteases 2

MeSH Terms

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
Claudins
Dextran Sulfate
Lactulose
Mannitol
Mannose-Binding Lectin
Sucrose
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