Alterations in gastric mucosal lineages induced by acute oxyntic atrophy in wild-type and gastrin-deficient mice

Sachiyo Nomura, Hirokazu Yamaguchi, Masako Ogawa, Timothy C. Wang, Jeffrey R Lee, James R. Goldenring

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

In addition to their role in gastric acid secretion, parietal cells secrete a number of growth factors that may influence the differentiation of other gastric lineages. Indeed, oxyntic atrophy is considered the most significant correlate with increased risk for gastric adenocarcinoma. We studied the alterations in gastric mucosal lineages elicited by acute oxyntic atrophy induced by treatment of C57BL/6 and gastrin-deficient mice with the parietal cell protonophore [S-(R*,S*)]-N-[1-(1,3-benzodioxol-5-yl)butyl]-3,3- diethyl-2-[4-[(4-methyl-1-piperazinyl)carbonyl]phenoxy]-4-oxo-1-azetidine carboxamide (DMP-777). In both wild-type and gastrin knockout mice, DMP-777 elicited the rapid loss of parietal cells within 2 days of treatment. In wild-type mice, oxyntic atrophy was accompanied by a rapid increase in 5-bromo-2′-deoxyuridine-labeled proliferative cells and attendant increase in surface cell numbers. However, gastrin knockout mice did not demonstrate significant foveolar hyperplasia and showed a blunted proliferative response. After 7 days of treatment in wild-type mice, a second proliferative population emerged at the base of fundic glands along with the development of a mucous cell metaplasia expressing TFF2/spasmolytic polypeptide (SPEM). However, in gastrin knockout mice, SPEM expressing both TFF2 mRNA and protein developed after only 1 day of DMP-777 treatment. In wild-type mice, all changes induced by DMP-777 were reversed 14 days after cessation of treatment. In gastrin-deficient mice, significant SPEM was still present 14 days after the cessation of treatment. The results indicate that foveolar hyperplasia requires the influence of gastrin, whereas SPEM develops in response to oxyntic atrophy independent of gastrin, likely through transdifferentiation of chief cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume288
Issue number2 51-2
DOIs
StatePublished - Feb 1 2005

Fingerprint

DMP 777
Gastrins
Atrophy
Stomach
Knockout Mice
Withholding Treatment
Hyperplasia
Cell Transdifferentiation
Gastric Acid
Metaplasia
Bromodeoxyuridine
Therapeutics
Intercellular Signaling Peptides and Proteins
Adenocarcinoma
Cell Count
Messenger RNA
Population

Keywords

  • Hyperplasia
  • Metaplasia
  • Spasmolytic polypeptide
  • Transdifferentiation
  • Trefoil proteins

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Alterations in gastric mucosal lineages induced by acute oxyntic atrophy in wild-type and gastrin-deficient mice. / Nomura, Sachiyo; Yamaguchi, Hirokazu; Ogawa, Masako; Wang, Timothy C.; Lee, Jeffrey R; Goldenring, James R.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 288, No. 2 51-2, 01.02.2005.

Research output: Contribution to journalArticle

Nomura, Sachiyo ; Yamaguchi, Hirokazu ; Ogawa, Masako ; Wang, Timothy C. ; Lee, Jeffrey R ; Goldenring, James R. / Alterations in gastric mucosal lineages induced by acute oxyntic atrophy in wild-type and gastrin-deficient mice. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2005 ; Vol. 288, No. 2 51-2.
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