Rabeprazole destroyed gastric epithelial barrier function through FOXF1/STAT3-mediated ZO-1 expression

Area of Science:

• Gastroenterology
• Molecular Biology
• Cell Biology

Background:

• Proton pump inhibitors like Rabeprazole are widely used for anti-ulcer treatment.
• The impact of Rabeprazole on gut barrier function is not fully understood.

Purpose of the Study:

• To investigate the effect of Rabeprazole on gut barrier function.
• To elucidate the underlying molecular mechanism involving ZO-1 expression and the FOXF1/STAT3 pathway.

Main Methods:

• Immunofluorescence (IF) analysis to assess ZO-1 expression.
• Western blotting (WB) and real-time PCR (qPCR) to quantify gene and protein expression.
• Investigated phosphorylation, nuclear translocation, and protein-protein interactions of FOXF1 and STAT3.

Main Results:

• Rabeprazole treatment significantly decreased ZO-1 expression in gastric epithelial cells.
• Rabeprazole inhibited the FOXF1/STAT3 pathway by reducing phosphorylation of STAT3 and FOXF1.
• This inhibition led to decreased nuclear translocation and binding of STAT3/FOXF1 to the ZO-1 promoter, disrupting barrier function.

Conclusions:

• Rabeprazole impairs gastric epithelial barrier function through the novel Rabeprazole/FOXF1/STAT3/ZO-1 pathway.
• Overexpression of STAT3 and FOXF1 can reverse Rabeprazole's inhibitory effects on ZO-1.
• Findings suggest a need for comprehensive consideration in Rabeprazole treatment regimens.