Targeted Apoptosis of Parietal Cells Is Insufficient to Induce Metaplasia in Stomach

Gastroenterology. 2017 Mar;152(4):762-766.e7. doi: 10.1053/j.gastro.2016.12.001. Epub 2016 Dec 5.

Abstract

Parietal cell atrophy is considered to cause metaplasia in the stomach. We developed mice that express the diphtheria toxin receptor specifically in parietal cells to induce their death, and found this to increase proliferation in the normal stem cell zone and neck but not to cause metaplastic reprogramming of chief cells. Furthermore, the metaplasia-inducing agents tamoxifen or DMP-777 still induced metaplasia even after previous destruction of parietal cells by diphtheria toxin. Atrophy of parietal cells alone therefore is not sufficient to induce metaplasia: completion of metaplastic reprogramming of chief cells requires mechanisms beyond parietal cell injury or death.

Keywords: Atp4b-Cre; CD44 Variant 9; Organoids; SPEM.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • Atrophy / chemically induced
  • Azetidines
  • Cell Proliferation
  • Cellular Reprogramming
  • Chief Cells, Gastric / metabolism
  • Chief Cells, Gastric / pathology*
  • Diphtheria Toxin / pharmacology
  • Heparin-binding EGF-like Growth Factor / genetics
  • Intercellular Signaling Peptides and Proteins
  • Intrinsic Factor / metabolism
  • Metaplasia / chemically induced
  • Metaplasia / genetics
  • Metaplasia / metabolism
  • Mice
  • Parietal Cells, Gastric / drug effects
  • Parietal Cells, Gastric / pathology*
  • Parietal Cells, Gastric / physiology*
  • Peptides / metabolism
  • Piperazines
  • Plant Lectins / metabolism
  • Stomach / pathology*
  • Tamoxifen

Substances

  • Azetidines
  • Diphtheria Toxin
  • Griffonia simplicifolia lectins
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Piperazines
  • Plant Lectins
  • spasmolytic polypeptide
  • Tamoxifen
  • DMP 777
  • Intrinsic Factor