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Loading of Mechanical Pressure Activates Mitogen-Activated Protein Kinase and Early Immediate Gene in Intestinal Epithelial Cells

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Abstract

Intestinal mucosa is continuously exposed to mechanical forces. We examined whether pressure loading activates mitogen-activated protein kinase (MAPK) and expression of early immediate genes in intestinal epithelial cells. Pressure was applied to IEC18 cells by helium gas in a culture flask and pressure-induced cell proliferation was examined. The expression of early immediate genes, MAPK activity, and activation of nuclear factor activator protein-1 (AP-1) were also examined. Pressures significantly promoted cell proliferation with peak effect at 80 mm Hg. Pretreatment with either a protein kinase C inhibitor or tyrosine kinase inhibitors, but not calcium chelating agents significantly inhibited cell proliferation promoted by pressure. Early inductions of c-myc and c-fos proteins, increased activity of MAPK, and activation of AP-1 were observed by pressure loading. Our study showed that intestinal mucosal cell proliferation is promoted by mechanical pressure and various intracellular signaling pathways are involved in the process.

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Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine, Keio University, Tokyo, 160-8582, Japan

    Masahiko Hirokawa & Hideo Yoshida

  2. Second Department of Internal Medicine, National Defense Medical College, Saitama, 359-8513, Japan

    Soichiro Miura

  3. Department of Internal Medicine, School of Medicine, Keio University, Tokyo, 160-8582, Japan

    Hiroshi Kishikawa, Hiromasa Nakamizo, Hajime Higuchi, Ruri C. Nakatsumi, Hidekazu Suzuki, Hidetsugu Saito & Hiromasa Ishii

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  1. Masahiko Hirokawa
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  2. Soichiro Miura
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  4. Hideo Yoshida
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  5. Hiromasa Nakamizo
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  6. Hajime Higuchi
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  10. Hiromasa Ishii
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Hirokawa, M., Miura, S., Kishikawa, H. et al. Loading of Mechanical Pressure Activates Mitogen-Activated Protein Kinase and Early Immediate Gene in Intestinal Epithelial Cells. Dig Dis Sci 46, 1993–2003 (2001). https://doi.org/10.1023/A:1010607819842

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