Document Detail

Urine-based detection of intestinal tight junction loss.
MedLine Citation:
PMID:  19525861     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Tight junction breakdown, with loss of the important sealing protein claudin-3, is an early event in the development of intestinal damage. Therefore, noninvasive analysis of intestinal tight junction status could be helpful in early detection of intestinal injury. AIM: To investigate the usefulness of urinary claudin-3 as marker for intestinal tight junction loss. METHODS: A rat hemorrhagic shock model and a human setting of known intestinal damage, that is, patients with relapsed inflammatory bowel disease (IBD), were used to investigate intestinal tight junction status by immunohistochemical staining and urinary claudin-3 levels by western blot. RESULTS: In rats claudin-3 urine levels increased rapidly after histologically proven intestinal tight junction loss, with significantly elevated levels at 90 minutes after shock compared with sham-operated animals [mean+/-SEM: 611+/-101 intensity (INT), n=6 vs. 232+/-30 INT, n=6; P<0.05]. Moreover, in colonic biopsies of patients with IBD relapse claudin-3 staining was reduced compared with biopsies of patients with IBD without signs of disease. Concomitantly, significantly increased claudin-3 urine levels were found in these patients (502+/-67 INT, n=10) compared with patients with IBD in remission (219+/-17 INT, n=10, P<0.001) and healthy volunteers (225+/-38 INT, n=10, P<0.001). CONCLUSION: Here we show for the first time in both an experimental and clinical setting a strong relation between intestinal tight junction loss and urinary claudin-3 levels. These findings suggest that measurement of urinary claudin-3 can be used as noninvasive marker for intestinal tight junction loss. This offers new opportunities for early diagnosis and follow-up of intestinal injury.
Geertje Thuijls; Joep P M Derikx; Jacco-Juri de Haan; Joep Grootjans; Adriaan de Bru?ne; Ad A M Masclee; Erik Heineman; Wim A Buurman
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of clinical gastroenterology     Volume:  44     ISSN:  1539-2031     ISO Abbreviation:  J. Clin. Gastroenterol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-22     Completed Date:  2010-03-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7910017     Medline TA:  J Clin Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e14-9     Citation Subset:  IM    
Department of Surgery, Maastricht University Medical Centre and Nutrition and Toxicology Research Institute Maastricht, The Netherlands.
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MeSH Terms
Biological Markers / urine
Blotting, Western
Disease Models, Animal
Inflammatory Bowel Diseases / physiopathology*
Intestines / metabolism*
Membrane Proteins / urine*
Middle Aged
Rats, Sprague-Dawley
Shock, Hemorrhagic / physiopathology
Tight Junctions / metabolism*
Young Adult
Reg. No./Substance:
0/Biological Markers; 0/Membrane Proteins; 0/claudin 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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