Altered gastric chief cell lineage differentiation in histamine-deficient mice

Koji Nozaki, Victoria Weis, Timothy C. Wang, A. Falus, James R. Goldenring

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The orderly differentiation of cell lineages within gastric glands is regulated by a complicated interplay of local mucosal growth factors and hormones. Histamine secreted from enterochromaffin-like cells plays an important role in not only stimulated gastric acid secretion but also coordination of intramucosal growth and lineage differentiation. We have examined histidine-decarboxylase (HDC)-deficient mice, which lack endogenous histamine synthesis, to evaluate the influence of histamine on differentiation of fundic mucosal lineages and the development of metaplasia following induction of acute oxyntic atrophy. Stomachs from HDC-deficient mice and wild-type mice were evaluated at 8 wk and 12 mo of age. DMP-777 was administrated orally to 6-wk-old mice for 1 to 14 days. Sections of gastric mucosa were stained with antibodies against Mist1, intrinsic factor, H/K-ATPase, trefoil factor 2 (TFF2), chromogranin A, and Ext1 and for the cell cycle marker phospho-histone H3. HDC-deficient mice at 8 wk of age demonstrated a prominent increase in chief cells expressing Mist1 and intrinsic factor. Importantly Mist1-positive mature chief cells were present in the midgland region as well as at the bases of fundic glands, indicating a premature differentiation of chief cells. Mice dually deficient for both HDC and gastrin showed a normal distribution of chief cells in fundic glands. Treatment of HDC-deficient mice with DMP-777 led to loss of parietal cells and an accelerated and exaggerated emergence of mucous cell metaplasia with the presence of dual intrinsic factor and TFF2-expressing cells throughout the gland length, indicative of the emergence of spasmolytic polypeptide-expressing metaplasia (SPEM) from chief cells. These findings indicate that histamine, in concert with gastrin, regulates the appropriate differentiation of chief cells from mucous neck cells as they migrate toward the bases of fundic glands. Nevertheless, histamine is not required for emergence of SPEM following acute oxyntic atrophy.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume296
Issue number6
DOIs
Publication statusPublished - Jun 2009

Fingerprint

Gastric Chief Cells
Cell Lineage
Histamine
Histidine Decarboxylase
Cell Differentiation
DMP 777
Metaplasia
Intrinsic Factor
Gastrins
Gastric Mucosa
Atrophy
Enterochromaffin-like Cells
Complement Factor H
Chromogranin A
Proton-Translocating ATPases
Normal Distribution
Gastric Acid
Histones
Growth Hormone
Intercellular Signaling Peptides and Proteins

Keywords

  • Enterochromaffin-like cell
  • Metaplasia
  • Spasmolytic polypeptide-expressing metaplasia

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Altered gastric chief cell lineage differentiation in histamine-deficient mice. / Nozaki, Koji; Weis, Victoria; Wang, Timothy C.; Falus, A.; Goldenring, James R.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 296, No. 6, 06.2009.

Research output: Contribution to journalArticle

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