Your browser doesn't support javascript.
loading
Rabeprazole destroyed gastric epithelial barrier function through FOXF1/STAT3-mediated ZO-1 expression.
Yang, Fangying; Li, Linkai; Zhou, Yanhe; Pan, Wenxu; Liang, Xinhua; Huang, Ling; Huang, Jing; Cheng, Yang; Geng, Lanlan; Xu, Wanfu; Gong, Sitang.
Afiliação
  • Yang F; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Li L; Department of Pharmacy, Zhuhai Center for Maternal and Child Health Care, Zhuhai, China.
  • Zhou Y; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Pan W; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Jinan University, Guangzhou, China.
  • Liang X; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Huang L; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Huang J; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Cheng Y; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Geng L; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Xu W; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Gong S; Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
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.
Assuntos
Palavras-chave

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

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