Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in Mongolian gerbils

Richard M. Peek, Hans Peter Wirth, Steven F. Moss, Manqiao Yang, A. M. Abdalla, Kyi T. Tham, Tong Zhang, Laura H. Tang, Irv M. Modlin, Martin J. Blaser

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Background and Aims: Human colonization with Helicobacter pylori increases the risk for distal gastric adenocarcinoma, possibly by altering gastric epithelial cell cycle events and/or gastrin secretion. This study aimed to determine whether H. pylori virulence-related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcinoma. Methods: Mongolian gerbils were challenged with H. pylori wild-type or isogenic cagA- and vacA- mutants, and apoptotic and proliferating cells were identified by terminal deoxynucleotidyl transferase- mediated deoxyuridine triphosphate nick-end labeling and proliferating cell nuclear antigen immunohistochemistry, respectively. Serum gastrin levels were determined by radioimmunoassay. Results: Gastric epithelial cell turnover was no different after infection with the wild-type, cagA-, or vacA- strains. H. pylori infection significantly increased antral apoptosis 2-4 weeks after challenge, before apoptotic indices decreased to baseline. In contrast, antral proliferation rates were significantly higher 16-20 weeks after inoculation, but then decreased by 40 weeks. Antral proliferation was significantly related to serum gastrin levels, whereas antral apoptosis was inversely related to acute inflammation and lymphoid follicles. Conclusions: In H. pylori-infected gerbils, enhanced antral apoptosis is an early and transient cell cycle event. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growth in H. pylori-colonized mucosa may be mediated by gastrin- dependent mechanisms.

Original languageEnglish (US)
Pages (from-to)48-59
Number of pages12
JournalGastroenterology
Volume118
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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