title: Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction.
abstract: BACKGROUND
  Integrity of the tight junction (TJ) which seals the gap between the epithelial cells of the gastrointestinal tract is critical in preventing the entry of the microbial toxins, antigens, and other harmful products in the subepithelial tissues and the internal milieu. By enabling the absorption of these products, impairment of the intestinal epithelial barrier leads to local and systemic inflammation. We have recently found depletion of the key protein constituents of colonic epithelial TJ in animals with chronic kidney disease (CKD). Postmortem studies have revealed the presence of inflammation throughout the gastrointestinal tract in uremic humans. This observation suggests that uremia may cause disruption of the epithelial barrier in all segments of the gastrointestinal tract including the stomach, jejunum, and ileum. The present study was undertaken to explore this possibility.
  
  
  METHODS
  Sprague-Dawley rats were randomized to CKD or control groups. The CKD group was subjected to 5/6 nephrectomy while the control group underwent a sham operation. The animals were observed for 10 weeks at which time they were euthanized and their stomachs, jejunums, and ileums were removed and processed for measurement of TJ proteins.
  
  
  RESULTS
  The CKD rats showed marked azotemia, systemic oxidative stress, and marked depletion of the key protein constituents of the epithelial TJ (claudin-1, occludin, and ZO1) in the stomach, jejunum, and ileum.
  
  
  CONCLUSIONS
  The present study extends the earlier finding of uremia-induced disruption of colonic epithelial TJ by documenting the involvement of the stomach, jejunum, and ileum as well.
authors.affiliation: Division of Nephrology and Hypertension, University of California, Irvine, Irvine, Calif. 92868, USA. ndvaziri@uci.edu
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Sohrab
authors.initials: S
authors.lastname: Nazertehrani
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Ni
authors.forename: Shuman
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D062445:Claudin-1 / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology*; D007249:Inflammation; D007421:Intestine, Small / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D062793:Occludin / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000503:physiopathology*; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000473:pathology*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062445:Claudin-1; C568114:Cldn1 protein, rat; D062793:Occludin; C568987:Ocln protein, rat; D062725:Tight Junction Proteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein