Rabeprazole destroyed gastric epithelial barrier function through FOXF1/STAT3‐mediated ZO‐1 expression. (22nd March 2023)

• Record Type: Journal Article
• Authors: Yang, Fangying; Li, Linkai; Zhou, Yanhe; Pan, Wenxu; Liang, Xinhua; Huang, Ling; Huang, Jing; Cheng, Yang; Geng, Lanlan; Xu, Wanfu; Gong, Sitang
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 50:Number 6(2023)
• Page Start: 516
• Page End: 526
• Publication Date: 2023-03-22
• Subjects: barrier function -- FOXF1 -- rabeprazole -- STAT3 -- ZO‐1; Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.13769
• Languages: English
• ISSNs: 0305-1870

Abstract

Abstract: 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.