Potentiation of Oxyntic Atrophy-Induced Gastric Metaplasia in Amphiregulin-Deficient Mice

KiTaek Nam, Andrea Varro, Robert J. Coffey, James R. Goldenring

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background & Aims: The loss of parietal cells from the gastric mucosa (oxyntic atrophy) is a critical step in the pathogenesis of chronic gastritis and gastric adenocarcinoma. Parietal cells are known to secrete epidermal growth factor receptor (EGFR) ligands, which are critical regulators of differentiation in the gastric mucosa. Although all of the actions of EGFR ligands are mediated through a common EGFR protein, individual ligands may produce different physiologic responses. Previous investigations have suggested that a deficit in EGFR signaling in waved-2 mice accelerates the emergence of metaplasia after induction of acute oxyntic atrophy. We sought to determine whether specific EGFR ligands regulate the metaplastic response to oxyntic atrophy. Methods: To induce spasmolytic polypeptide-expressing metaplasia (SPEM), amphiregulin (AR) and transforming growth factor-α-deficient mice and their wild-type littermates were treated with DMP-777 for 0-14 days and for 14 days followed by 14 days of recovery off drug. We evaluated the gastric mucosal response to oxyntic atrophy using cell lineage-specific markers. Results: Although loss of transforming growth factor-α did not influence the induction of SPEM, loss of AR caused an acceleration and amplification in the induction of SPEM after acute oxyntic atrophy. Trefoil factor family 2/spasmolytic polypeptide and intrinsic factor dual-immunostaining cells significantly increased in the SPEM of AR-deficient mice. At the bases of glands, intrinsic factor immunoreactive cells also were costained for 5-bromo-2'-deoxyuridine, suggesting their re-entry into the cell cycle. Conclusions: The absence of AR promoted the rapid emergence of SPEM in response to oxyntic atrophy.

Original languageEnglish
Pages (from-to)1804-1819
Number of pages16
JournalGastroenterology
Volume132
Issue number5
DOIs
Publication statusPublished - 2007 Jan 1

Fingerprint

Metaplasia
Atrophy
Stomach
Epidermal Growth Factor Receptor
Ligands
Intrinsic Factor
DMP 777
Transforming Growth Factors
Gastric Mucosa
Cell Lineage
Gastritis
Bromodeoxyuridine
Amphiregulin
spasmolytic polypeptide
Cell Cycle
Adenocarcinoma
Pharmaceutical Preparations
Proteins

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Nam, KiTaek ; Varro, Andrea ; Coffey, Robert J. ; Goldenring, James R. / Potentiation of Oxyntic Atrophy-Induced Gastric Metaplasia in Amphiregulin-Deficient Mice. In: Gastroenterology. 2007 ; Vol. 132, No. 5. pp. 1804-1819.
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Potentiation of Oxyntic Atrophy-Induced Gastric Metaplasia in Amphiregulin-Deficient Mice. / Nam, KiTaek; Varro, Andrea; Coffey, Robert J.; Goldenring, James R.

In: Gastroenterology, Vol. 132, No. 5, 01.01.2007, p. 1804-1819.

Research output: Contribution to journalArticle

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T1 - Potentiation of Oxyntic Atrophy-Induced Gastric Metaplasia in Amphiregulin-Deficient Mice

AU - Nam, KiTaek

AU - Varro, Andrea

AU - Coffey, Robert J.

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