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Transmural Pressure Loading Enhances Gastric Mucosal Cell Proliferation

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Abstract

Aim

Although increased intraluminal pressure in the stomach due to gastric outlet obstruction or functional gastric motor dysfunction, including gastroparesis, may affect gastric mucosal integrity, the direct effect of mechanical pressure on gastric mucosal cells has not yet been fully investigated. The aims of this study were to determine whether exposure to transmural pressure would affect the proliferation of gastric mucosal cells and to elucidate the intracellular signaling pathways involved.

Methods

Cellular proliferation and DNA synthesis were evaluated in rat gastric epithelial cells exposed to high transmural pressures. The levels of activation of 3 MAP kinases, ERK, JNK, and p38, were assessed, and the induction of immediate early gene expression was examined. The activation of nuclear factor activator protein-1 (AP-1) was evaluated by an electrophoretic mobility shift assay.

Results

Exposure to high transmural pressure significantly increased DNA synthesis within 24 h, with the most marked increase observed after exposure to a pressure of 80 mmHg, and this increase was inhibited by the MEK1 inhibitor PD98059. Early activation of ERK kinase, but not of JNK or p38 kinase, was detected after pressure loading. Early induction of the c-fos and c-myc genes and activation of the AP-1 transcription factor were also demonstrated within 3 h of exposure to 80 mmHg of pressure.

Conclusion

Gastric mucosal cell proliferation induced by exposure to high transmural pressure may be related to early activation of ERK, the induction of c-fos and c-myc, and the activation of AP-1.

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (no. 22300169, to HS), a Health and Labour Sciences Research Grant for Research on Health Technology Assessment (Clinical Research Promotion no. 47 to HS), a grant from the Smoking Research Foundation (to HS), the Keio Gijuku Academic Development Fund (to HS) and National Defense Medical College.

Conflict of interest

None.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Hiromasa Nakamizo, Hidekazu Suzuki, Sachiko Mogami, Hiroshi Kishikawa, Hideo Yoshida & Toshifumi Hibi

  2. Second Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan

    Soichiro Miura

  3. Division of Clinical Medicine, Faculty of Medical Sciences, University of Tsukuba, Tsukuba, Japan

    Hirofumi Matsui

Authors
  1. Hiromasa Nakamizo
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  2. Hidekazu Suzuki
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  3. Soichiro Miura
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  4. Sachiko Mogami
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  5. Hiroshi Kishikawa
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  6. Hideo Yoshida
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  7. Hirofumi Matsui
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  8. Toshifumi Hibi
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Correspondence to Hidekazu Suzuki.

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Nakamizo, H., Suzuki, H., Miura, S. et al. Transmural Pressure Loading Enhances Gastric Mucosal Cell Proliferation. Dig Dis Sci 57, 2545–2554 (2012). https://doi.org/10.1007/s10620-012-2208-2

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  • DOI: https://doi.org/10.1007/s10620-012-2208-2

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