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This Article Full Text Full Text (PDF) All Versions of this Article: 290/4/G793    most recent 00309.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Ogawa, M. Articles by Goldenring, J. R. Search for Related Content PubMed PubMed Citation Articles by Ogawa, M. Articles by Goldenring, J. R.

MUCOSAL BIOLOGY

Altered metaplastic response of waved-2 EGF receptor mutant mice to acute oxyntic atrophy

Departments of ¹Surgery and ²Cell and Developmental Biology, Vanderbilt University School of Medicine, and ³Nashville Department of Veterans Affairs Medical Center, Nashville, Tennessee; ⁴Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; ⁵Physiological Laboratory, University of Liverpool, Liverpool, United Kingdom; and ⁶Columbia-Presbyterian Medical Center, New York, New York

Submitted 7 July 2005 ; accepted in final form 11 November 2005

Metaplastic cell lineages are putative precursors for the development of gastric adenocarcinoma. The loss of parietal cells (oxyntic atrophy) is the initiating step in the evolution of gastric fundic mucosal lineage changes including metaplasia and hyperplasia. However, the intrinsic mucosal factors that promote and modulate the emergence of metaplastic phenotypes remain obscure. Over the past several years, we have studied pharmacologically induced, reversible oxyntic atrophy in rodents treated with DMP-777, a drug that acts as a parietal cell secretory membrane protonophore. DMP-777 elicits a rapid loss of parietal cells followed by the emergence of foveolar hyperplasia and spasmolytic polypeptide (SP)-expressing metaplasia (SPEM). The objective of the present study was to provide further insights into the intrinsic mucosal factors regulating the emergence of SPEM in the setting of oxyntic atrophy. We therefore studied the effects of DMP-777 administration on both SP/trefoil factor (TFF)2-deficient mice, which lack SP/TFF2, a marker of SPEM, and waved-2 mice, which harbor a point mutation in the EGF receptor that attenuates its tyrosine kinase activity. As in wild-type mice, treatment with DMP-777 for 7 days did elicit SPEM in SP/TFF2-deficient mice. These results suggest that SP/TFF2 does not impact on the development of metaplasia after the induction of parietal cell loss. In contrast, waved-2 homozygous mice displayed accelerated SPEM development by 3 days of treatment with DMP-777. These findings indicate that attenuation of EGF receptor signaling in waved-2 mice does elicit a more rapid emergence of SPEM. The results support a role for EGF receptor ligands in the regulation of gastric metaplasia.

metaplasia; trefoil factors; gastritis; epidermal growth factor receptor; gastrin

This article has been cited by other articles:

				K. Nozaki, V. Weis, T. C. Wang, A. Falus, and J. R. Goldenring Altered gastric chief cell lineage differentiation in histamine-deficient mice Am J Physiol Gastrointest Liver Physiol, June 1, 2009; 296(6): G1211 - G1220. [Abstract] [Full Text] [PDF]

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