title: Melatonin protects the esophageal epithelial barrier by suppressing the transcription, expression and activity of myosin light chain kinase through ERK1/2 signal transduction.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Tan
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.forename: Nina
authors.initials: N
authors.lastname: Zhang
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Sun
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008875:Middle Aged; D009219:Myosin-Light-Chain Kinase / Q000096:biosynthesis / Q000235:genetics*; D019108:Tight Junctions / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D009219:Myosin-Light-Chain Kinase; D008550:Melatonin