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Rebamipide, a Gastroprotective Drug, Inhibits Indomethacin-Induced Apoptosis in Cultured Rat Gastric Mucosal Cells: Association with the Inhibition of Growth Arrest and DNA Damage-Induced 45α Expression

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Abstract

Rebamipide, a gastromucosal protective drug, suppresses indomethacin-induced gastropathy in humans and rodents. Effects of rebamipide on gene expression in indomethacin-treated gastric mucosal cells (RGM1) were investigated using high-density oligonucleotide arrays. Indomethacin induced apoptosis in RGM1 cells in a dose-dependent manner. Rebamipide pretreatment significantly reduced indomethacin-induced apoptosis. We used gene expression profiling on high-density oligonucleotide probe arrays to characterize the transcriptional response of RGM1 cells to indomethacin treatment for 6 hr. Of the 8,799 probes examined, 717 (8.1%) were induced (400 probes) or repressed (317 probes) at least 1.5-fold. Among the 158 genes that were induced by indomethacin at least 2.0-fold, four genes that were down-regulated by rebamipide at least 2.0-fold are listed: growth arrest and DNA-damage-inducible 45α (GADD45α), golgi SNAP receptor complex member 1, iodothyronine deiodinases, and transcription factor 8. Real time-PCR confirmed GADD45α expression and its inhibition by rebamipide. Inhibition of apoptosis-related genes is possibly important for the cytoprotective effect of rebamipide against indomethacin-induced gastric mucosal cell injury.

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Authors and Affiliations

  1. Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Yuji Naito MD, PhD & Norimasa Yoshida MD, PhD

  2. Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566

    Hirokazu Kajikawa MD, Katsura Mizushima, Makoto Shimozawa MD, Masaaki Kuroda MD, Kazuhiro Katada MD, PhD, Tomohisa Takagi MD, PhD & Toshikazu Yoshikawa MD, PhD

  3. Department of Biomedical Safety Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566

    Osamu Handa MD, PhD & Satoshi Kokura MD, PhD

  4. Department of Food Sciences and Nutritional Health, The Faculty of Human Environment, Kyoto Prefectural University, Kyoto, 606-8522

    Hiroshi Ichikawa MD, PhD

  5. Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan

    Hirofumi Matsui MD, PhD

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  1. Yuji Naito MD, PhD
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  2. Hirokazu Kajikawa MD
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  10. Hiroshi Ichikawa MD, PhD
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  11. Norimasa Yoshida MD, PhD
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  12. Hirofumi Matsui MD, PhD
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Correspondence to Yuji Naito MD, PhD.

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Naito, Y., Kajikawa, H., Mizushima, K. et al. Rebamipide, a Gastroprotective Drug, Inhibits Indomethacin-Induced Apoptosis in Cultured Rat Gastric Mucosal Cells: Association with the Inhibition of Growth Arrest and DNA Damage-Induced 45α Expression. Dig Dis Sci 50 (Suppl 1), S104–S112 (2005). https://doi.org/10.1007/s10620-005-2814-3

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  • DOI: https://doi.org/10.1007/s10620-005-2814-3

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