ERK1/2 participates in regulating the expression and distribution of tight junction proteins in the process of reflux esophagitis

OBJECTIVE: To investigate the alterations of esophageal epithelial barrier during the process of reflux esophagitis (RE). METHODS: In total, 85 Sprague-Dawley rats were randomly divided into two groups, the sham-operation group (n = 25) and the RE group induced by incomplete pyloric ligation (n = 60). The establishment of RE model and the severity of esophagitis were evaluated by hematoxylin and eosin stain. Dilated intercellular spaces (DIS) in the esophageal epithelium were observed by transmission electron microscopy. The cellular distributions of ZO-1, occludin and claudin-1 were assessed by immunohistochemical stain. The expressions of these tight junction (TJ) proteins and the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), myosin light chain (MLC) and nonmuscular myosin light chain kinase (nmMLCK) were analyzed by Western blot. RESULTS: DIS occurred gradually in the RE group. ZO-1, occludin and claudin-1 were incompletely or even not expressed in the RE group. TJ proteins were expressed in the membrane instead of the cytoplasm in many epithelial cells in RE. With Western, the expression of ZO-1, occludin and claudin-1 was increased gradually in the RE group (P < 0.05). The phosphorylation levels of nmMLCK, MLC and ERK1/2 were also increased (P < 0.05). There was no marked changes in the esophageal epithelium in the sham-operation group. CONCLUSIONS: TJ proteins could be used as sensitive markers of RE instead of DIS. ERK1/2 may participate in regulating TJ proteins in esophageal epithelia in RE.