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

• Published in: Journal of gastroenterology Vol. 40; no. 8; pp. 781 - 790
• Main Authors: Asaoka, Daisuke, Miwa, Hiroto, Hirai, Shu, Ohkawa, Akimitsu, Kurosawa, Akihiko, Kawabe, Masato, Hojo, Mariko, Nagahara, Akihito, Minoo, Toshoku, Ohkura, Ryuichi, Ohkusa, Toshifumi, Sato, Nobuhiro
• Format: Journal Article
• Language: English
• Published: Japan Springer Nature B.V 01.08.2005
• Subjects: 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
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-005-1628-6

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. 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. 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. 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.