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.


CONCLUSIONS
EGF and ZO-1 play significant roles in esophageal epithelial defense against acid.
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abenoku, Osaka, Japan.
Masatsugu
M
Okuyama
Yasuhiro
Y
Fujiwara
Tetsuya
T
Tanigawa
Kenji
K
Watanabe
Kenji
K
Watababe
Masatsugu
M
Shiba
Kazunari
K
Tominaga
Toshio
T
Watanabe
Toshio
T
Watanebe
Nobuhide
N
Oshitani
Kazuhide
K
Higuchi
Tetsuo
T
Arakawa
D000704:Analysis of Variance; D015153:Blotting, Western; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006851:Hydrochloric Acid; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects* / Q000378:metabolism*; D019108:Tight Junctions; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D004815:Epidermal Growth Factor; D006851:Hydrochloric Acid