Regulation of gastric epithelial cell development revealed in H+/K+-ATPase β-subunit- and gastrin-deficient mice

Teo V. Franic, Louise M. Judd, David Robinson, Simon P. Barrett, Katrina L. Scarff, Paul A. Gleeson, Linda C. Samuelson, Ian R. Van Driel

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Abstract

The gastric H+/K+-ATPase is essential for normal development of parietal cells. Here we have directly assessed the role of the H+/K+-ATPase β-subunit (H/K-β) on epithelial cell development by detailed quantitation of the epithelial cell types of the gastric mucosa of H/K-β-deficient mice. H/K-β-deficient mice had a 3.1-fold increase in the number of immature cells per gastric unit; however, the numbers of surface mucous and parietal cells were similar to those in the gastric units of wild-type mice. The effect of elevated gastrin levels in the H/K-β-deficient mice was determined by producing mice that are also deficient in gastrin. We demonstrated that the increased production of immature cells and resulting hypertrophy is caused by the overproduction of gastrin. However, the depletion of zymogenic cells, which is another feature of H/K-β-deficient mice, is independent of hypergastrinemia. Significantly, parietal cells of H/K-β- and gastrin-deficient mice had abnormal secretory membranes and were devoid of resting tubulovesicular membranes. Together these data suggest a homeostatic mechanism limiting the number of immature cells that can develop into end-stage epithelial cells and indicate a direct role for H/K-β in the development of mature parietal cells.

Original languageEnglish
Pages (from-to)G1502-G1511
Number of pages10
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Volume281
Issue number6
DOIs
Publication statusPublished - Dec 2001

Keywords

  • Gastric mucosa
  • Membrane biosynthesis
  • Parietal cell

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