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Alterations in Gastric Mucosal Lineages Before or After Acute Oxyntic Atrophy in Gastrin Receptor and H2 Histamine Receptor-Deficient Mice

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Abstract

Spasmolytic polypeptide (SP/TFF2)-expressing metaplasia (SPEM) is induced by oxyntic atrophy and is known as a precancerous or paracancerous lesion. We seek to determine whether the gastrin receptor or H2 histamine receptor influence the development of SPEM. DMP-777 was administered to gastrin receptor and/or H2 receptor-deficient mice and wild-type mice. Gastric mucosal lineage changes were analyzed. The mucosa from double knockout mice and H2 receptor knockout mice contained elevated numbers of dual TFF2 and intrinsic factor immunoreactive cells even before DMP-777 treatment. All genotypes of mice showed SPEM after 7-day treatment. In all types of knockout mice, the number of TFF2 immunoreactive cells remained elevated after cessation of treatment. The H2 receptor and gastrin receptor do not affect emergence of SPEM. However, it is suggested that the absence of H2 receptor signaling causes a delay in the maturation of chief cells from mucous neck cells.

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Acknowledgments

We thank Dr. N. Wright, Dr. David Alpers, and Dr. Adam Smolka for gifts of antibodies. This work was supported in part by a Merit Review Award to J.R.G. from the Department of Veterans Affairs. This work was also supported in part by Grants-in-Aid for scientific Research to S.N. from the Japan Society for Promotion of Science.

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Susumu Aikou, Masako Ogawa, Koji Nozaki & Sachiyo Nomura

  2. Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Yasushi Fukushima

  3. Department of Internal Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan

    Toshihito Saito

  4. Hematology/Oncology, Department of Medicine, Kobe University Graduate of Medicine, Kobe, Japan

    Toshimitsu Matsui

  5. Nashville VA Medical Center, Departments of Surgery and Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA

    James R. Goldenring

  6. Showa General Hospital, Tokyo, Japan

    Michio Kaminishi

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  1. Susumu Aikou
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  2. Yasushi Fukushima
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  3. Masako Ogawa
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  4. Koji Nozaki
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  5. Toshihito Saito
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  6. Toshimitsu Matsui
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  7. James R. Goldenring
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  8. Michio Kaminishi
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  9. Sachiyo Nomura
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Correspondence to Sachiyo Nomura.

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Aikou, S., Fukushima, Y., Ogawa, M. et al. Alterations in Gastric Mucosal Lineages Before or After Acute Oxyntic Atrophy in Gastrin Receptor and H2 Histamine Receptor-Deficient Mice. Dig Dis Sci 54, 1625–1635 (2009). https://doi.org/10.1007/s10620-009-0832-2

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  • DOI: https://doi.org/10.1007/s10620-009-0832-2

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