Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis
Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis
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DOI：
10.1007/s00535-005-1628-6
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发表时间：
2005-08-01
影响因子：
6.3
通讯作者：
Sato, N
中科院分区：
文献类型：
--
作者：
Asaoka, D;Miwa, H;Sato, N
背景：食管紧密连接负责上皮的细胞旁密封。紧密连接蛋白表达的改变在某些人类疾病的发病机制中起着至关重要的作用。本研究的目的是调查的分布和表达模式的紧密连接蛋白在对照组大鼠和大鼠反流性食管炎。方法：慢性酸反流性食管炎大鼠实验性手术诱导。术后第7天和第14天处死动物。观察粘膜厚度和5-溴-2-脱氧尿苷（BrdU）标记指数。免疫荧光染色和Western blotting法检测对照组和食管炎大鼠食管黏膜紧密连接蛋白claudin 1-4和occludin的表达。在对照组大鼠中，claudin-1、-3和-4定位于食管上皮细胞的细胞膜上，主要在棘层和颗粒层中，而claudin-2在任何层中均未检测到。在所有食管粘膜层的细胞膜上均可见Occludin。在食管炎大鼠中，claudin-1在棘层和颗粒层糜烂周围的质膜和细胞质中的表达均增加。claudin-4和occludin的表达从棘层和颗粒层的质膜转移到细胞质。结论：对照组和大鼠食管炎模型中紧密连接蛋白的定位和表达模式不同。食管粘膜中claudin-3的表达减少，而claudin-1的表达增加。据推测，紧密连接蛋白的这些改变最有可能增加食管上皮的通透性，从而损害该上皮的防御机制。
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.