Document Detail

Evidence for tight junction protein disruption in intestinal mucosa of malignant obstructive jaundice patients.
MedLine Citation:
PMID:  20095884     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain obscure. Integrated tight junctions (TJs) are essential for normal gut barrier function. TJ proteins, such as zonula occludens (ZO)-1, claudins and occludin, are indispensable to maintain the function of TJs. This study was undertaken to investigate whether TJ protein disruption occurs in the intestinal mucosa of malignant obstructive jaundice (MOJ) patients. MATERIAL AND METHODS: Three groups were involved: Group A, MOJ patients whose bilirubin level was >or= 43 microM; Group B, MOJ patients without jaundice; and Group C, patients who underwent gastroscopy with negative findings (controls). Biopsy was done in all participants at the second part of the duodenum, distal to the ampulla of Vater. The morphological and ultrastructural changes of intestinal mucosa were observed. The distributions and expressions of the TJ proteins occludin, ZO-1, claudin-1 and claudin-4 in intestinal mucosa were evaluated by immunohistochemistry and Western blotting. RESULTS: Histological examination showed a mild infiltration of the lamina propria by chronic inflammatory cells in Group A compared with Groups B and C. Duodenal architecture showed that the microvillus of Group A patients was loose, the structures of junctional complexes were disrupted and the gaps between cell junctions were wider. As shown by immunohistochemical staining and Western blotting, greatly reduced expressions of occludin, ZO-1 and claudin-1 protein were detected in Group A, whereas claudin-4 expression was significantly increased. CONCLUSIONS: TJs in MOJ patients with jaundice were disrupted in the intestinal epithelium, which may have resulted from the alterations in TJ-related protein expression. TJ interruption may be a key factor contributing to intestinal mucosal barrier injury and increased intestinal permeability.
Na Wang; Huiling Yu; Junji Ma; Wenxin Wu; Dongqiang Zhao; Xiaodong Shi; Hui Tian; Huiqing Jiang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of gastroenterology     Volume:  45     ISSN:  1502-7708     ISO Abbreviation:  Scand. J. Gastroenterol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-01-25     Completed Date:  2010-03-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0060105     Medline TA:  Scand J Gastroenterol     Country:  England    
Other Details:
Languages:  eng     Pagination:  191-9     Citation Subset:  IM    
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei, China.
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MeSH Terms
Bilirubin / metabolism
Claudins / metabolism
Duodenum / pathology
Intestinal Mucosa / metabolism*,  pathology,  ultrastructure
Jaundice, Obstructive / metabolism*,  pathology
Membrane Proteins / metabolism*
Middle Aged
Phosphoproteins / metabolism
Tight Junctions / metabolism*
Reg. No./Substance:
0/Claudins; 0/Membrane Proteins; 0/Phosphoproteins; 0/occludin; 0/zonula occludens-1 protein; 635-65-4/Bilirubin

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