Loss of carbonic anhydrase IX expression impairs gastric mucosal defence against luminal acid (1109.13)

Abstract

Background: The exoenzyme carbonic anhydrase IX is strongly expressed in tumours. In normal tissues, CA IX is expressed during embryogenesis but downregulated postnatally, except in the stomach. Aim and Methods: We studied the cellular differentiation pattern and acid secretory capacity in gastric mucosa from CAIX KO and WT mice at age 8 days to 1,3,6,9,12 months. Surface pH and mucus layer thickness, as well as the ability of the surface epithelial cells to withstand a luminal acid load was assessed in young adult CAIX KO and WT mice by in vivo two photon microscopy. Results: CAIX KO gastric mucosa developed a unique phenotype with a gradual expansion of the surface cell zone, and regression of the parietal cell zone to the lower gland area. Concomitantly, the acid secretory capacity, which was normal at young age, declined. HCO3‐ output into the lumen and mucus layer thickness were not significantly different between CAIX KO and WT. However, the ability of the surface cells to withstand a luminal acid load, as well as to maintain a more alkaline surface pH than the luminal pH, was significantly impaired in CAIX KO compared to WT stomach. Conclusion: We speculate that the CAIX at the basolateral membrane of the gastric surface cells rapidly converts extruded protons with blood‐borne HCO3‐ to CO2 and thus augments interstitial buffer capacity, surface cell pHi regulation, and maintenance of the pH microclimate in the mucus layer.Grant Funding Source: Supported by DFG Se 13‐4 and 9‐6 to Ursula Seidler