Roles of ZO-1 and epidermal growth factor in esophageal epithelial defense against acid

Background: The tight junction plays a crucial role in structural esophageal epithelial defenses that maintain esophageal epithelial integrity. We examined the roles of ZO-1 and epidermal growth factor (EGF) in esophageal epithelial defense against acid using human esophageal epithelial cells. Methods: Human esophageal epithelial cells (TE- 1) were incubated with acidified medium in the presence or absence of various doses of EGF. We examined cell viability, expression and localization of ZO-1, and epithelial barrier functions such as transepithelial resistance and paracellular flux using fluorescein isothiocyanate (FITC)-conjugated dextran. Results: TE-1 cells expressed ZO-1 and immunofluorescence detection of ZO-1 revealed continuous pericellular labeling of the epithelial monolayer. Acidified medium, which did not affect cell viability, reduced ZO-1 expression and yielded a discontinuous and fragmented pattern of expression, and also reduced transepithelial resistance and increased paracellular flux of FITC-dextran. EGF did not affect ZO-1 expression and epithelial barrier function under normal condition, while EGF significantly inhibited reduction of ZO-1 expression in a dose-dependent manner, and also inhibited impairment of barrier functions by acid exposure. Conclusion: EGF and ZO-1 play significant roles in esophageal epithelial defense against acid.