Evidence for tight junction protein disruption in intestinal mucosa of malignant obstructive jaundice patients.
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.


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.
Wang
Na
N
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei, China.
Yu
Huiling
H
Ma
Junji
J
Wu
Wenxin
W
Zhao
Dongqiang
D
Shi
Xiaodong
X
Tian
Hui
H
Jiang
Huiqing
H
D000368:Aged; D001663:Bilirubin / Q000378:metabolism; D057167:Claudins / Q000378:metabolism; D004386:Duodenum / Q000473:pathology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D041781:Jaundice, Obstructive / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D062793:Occludin; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D001663:Bilirubin