Melatonin Protects the Esophageal Epithelial Barrier by Suppressing the Transcription, Expression and Activity of Myosin Light Chain Kinase Through ERK1/2 Signal Transduction

作者：Tan, Jiacheng; Wang, Ying; Xia, Yang; Zhang, Nina; Sun, Xiaomeng; Yu, Ting; Lin, Lin^*

来源：Cellular Physiology and Biochemistry, 2014, 34(6): 2117-2127.

DOI：10.1159/000369656

• Melatonin
• Esophageal epithelial barrier
• Myosin light chain kinase

Background/Aims: Dilated intercellular space (DIS) contributes to the pathophysiology of gastroesophageal reflux disease (GERD). Melatonin protects the esophageal mucosa; however, the mechanisms underlying that protection remain unclear. Methods: Transmission electron microscopy (TEM) was used to evaluate the intercellular spaces in the esophageal epithelium of GERD patients. The Het-1A monolayer barrier function was investigated by measuring transepithelial resistance (TER) and FITC-dextran paracellular permeation. The activity of MLCK was represented by MLC phosphorylation. The expression and phosphorylation of MLCK, MLC and ERK were examined by western blot analysis. Results: The expression and activity of MLCK and ERK phosphorylation were increased in the esophageal epithelium. The increased expression and activity of MLCK was correlated with dilated intercellular spaces. Upon acid treatment, the Het-1A monolayer permeability was increased. When the Het-1A monolayer was pretreated with melatonin and PD98059 before the acid incubation, the permeability and the expression and phosphorylation of MLCK and ERK decreased. Conclusion: Melatonin protects the esophageal epithelial barrier by suppressing the transcription, translation and activity of MLCK through ERK1/2 signal transduction. These findings provide a better understanding of the potential clinical application of melatonin in GERD treatment.

• 出版日期2014
• 单位南京医科大学