Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis

J Gastroenterol. 2005 Aug;40(8):781-90. doi: 10.1007/s00535-005-1628-6.


Background: The esophageal tight junction is responsible for the paracellular sealing of the epithelium. Alteration of the expression of tight-junction proteins plays crucial roles in the pathogenesis of some human diseases. The aim of this study was to investigate the distribution and expression pattern of tight-junction proteins in the esophageal mucosa of control rats and rats with reflux esophagitis.

Methods: Chronic acid reflux esophagitis was experimentally induced by operation in rats. The animals were killed on days 7 and 14 after the operation. The thickness of the mucosa and the 5-bromo-2-deoxyuridine (BrdU) labeling index were assessed. The expression pattern of the tight-junction proteins claudin 1-4 and occludin in the esophageal mucosa was investigated by immunofluorescence staining and Western blotting in the controls and esophagitis rats.

Results: In the esophagitis model, the thickness and BrdU labeling index increased with time. In control rats, claudin-1, -3, and -4 were localized on the cellular membranes of esophageal epithelial cells, mainly in the spinous and granular layers, while claudin-2 was not detected in any layer. Occludin was seen on the cellular membranes in all esophageal mucosal layers. In the esophagitis rats, the expression of claudin-1 was increased both in the plasma membrane and in the cytoplasm around the erosion in the spinous and granular layers. The expression of claudin-4 and occludin shifted to the cytoplasm from the plasma membrane in the spinous and granular layers. In contrast, the expression of claudin-3 was decreased in the spinous and granular layers.

Conclusions: The localization and the expression patterns of tight-junction proteins were different in the controls and the rat esophagitis model. The expression of claudin-3 in the esophageal mucosa was decreased, while that of claudin-1 was increased. It is postulated that these alterations in tight-junction proteins most likely increase the permeability of the esophageal the epithelium, thereby impairing the defense mechanism of this epithelium.

MeSH terms

  • Animals
  • Blotting, Western
  • Chronic Disease
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudins
  • Disease Models, Animal
  • Esophagitis, Peptic / metabolism*
  • Fluorescent Antibody Technique
  • Membrane Proteins / analysis*
  • Mucous Membrane / chemistry
  • Occludin
  • Rats


  • CLDN1 protein, human
  • CLDN3 protein, human
  • CLDN4 protein, human
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudins
  • Cldn1 protein, rat
  • Cldn2 protein, rat
  • Cldn3 protein, rat
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Ocln protein, rat