Genetic ablation of carbonic anhydrase IX disrupts gastric barrier function via claudin-18 downregulation and acid backflux.

ABSTRACT:

Aim

This study aimed to explore the molecular mechanisms for the parietal cell loss and fundic hyperplasia observed in gastric mucosa of mice lacking the carbonic anhydrase 9 (CAIX).

Methods

We assessed the ability of CAIX-knockout and WT gastric surface epithelial cells to withstand a luminal acid load by measuring the pH_i of exteriorized gastric mucosa in vivo using two-photon confocal laser scanning microscopy. Cytokines and claudin-18A2 expression was analysed by RT-PCR.

Results

CAIX-knockout gastric surface epithelial cells showed significantly faster pH_i decline after luminal acid load compared to WT. Increased gastric mucosal IL-1β and iNOS, but decreased claudin-18A2 expression (which confer acid resistance) was observed shortly after wea

SUBMITTER: Li T 

PROVIDER: S-EPMC5901031 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature