Rabeprazole destroyed gastric epithelial barrier function through FOXF1/STAT3-mediated ZO-1 expression.
Clin Exp Pharmacol Physiol
; 50(6): 516-526, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-36897043
Rabeprazole is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, the effect of Rabeprazole on gut barrier function remains to be identified. In this study, we show that ZO-1 expression is decreased in patients receiving Rabeprazole by immunofluorescence (IF) analysis. Western blotting (WB) and real-time PCR (qPCR) results demonstrate that Rabeprazole treatment leads to a significant downregulation of ZO-1 expression through inhibition of the FOXF1/STAT3 pathway, leading to destroy barrier function, which illustrates a novel pathway that Rabeprazole regulates barrier function in gastric epithelial cells. Mechanistically, Rabeprazole treatment led to a downregulation of STAT3 and FOXF1 phosphorylation, leading to inhibit nuclear translocation and decrease the binding of STAT3 and FOXF1 to ZO-1 promoter, respectively. Most important, endogenous FOXF1 interacted with STAT3, and this interaction was dramatically abolished by Rabeprazole stimulation. Overexpression of STAT3 and FOXF1 in GES-1 cells reversed the inhibitory effect of Rabeprazole on ZO-1 expression, respectively. These finding extended the function of Rabeprazole and established a previously unappreciated mechanism by which the Rabeprazole/FOXF1/STAT3 axis facilitated ZO-1 expression to regulate barrier function, and a comprehensive consideration and evaluation was required in treatment of patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Células Epiteliais
/
Rabeprazol
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China