The role of Klotho, anti-aging molecule, in chronic gastritis and gastric carcinogenesis

• Project/Area Number: 23590925
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka City University
• Principal Investigator: TANIGAWA Tetsuya 大阪市立大学, 医学(系)研究科(研究院), 講師 (70423879)
• Co-Investigator(Kenkyū-buntansha): WATANABE Toshio 大阪市立大学, 大学院医学研究科, 准教授 (50336773) ; TOMINAGA Kazunari 大阪市立大学, 大学院医学研究科, 准教授 (80336768) ; FUJIWARA Yasuhiro 大阪市立大学, 大学院医学研究科, 准教授 (40285292) ; MACHIDA Hirohisa 大阪市立大学, 大学院医学研究科, 医員 (00382078) ; ARAKAWA Tetsuo 大阪市立大学, 大学院医学研究科, 教授 (60145779)
• Research Collaborator: OTANI Koji 大阪市立大学, 大学院医学研究科, 研究医
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: Klotho / ヘリコバクター・ピロリ / 萎縮性胃炎 / 胃潰瘍 / TLR9 / 胃発がん / 炎症 / 老化 / Helicobacter pylori / 胃癌 / 細胞増殖 / 創傷治癒 / 消化管上皮 / 慢性胃炎 / klotho

Research Abstract

The klotho gene was originally identified as an aging suppressor gene. We investigated whether Klotho is involved in pathophysiology in the stomach diseases. (Study 1) Gastric ulcer is associated with Helicobacter pylori (Hp) infection. During gastric ulcer healing, expression of mRNA for Klotho in gastric epithelial cells at the ulcer margin was reduced compared with normal gastric tissue. Administration of recombinant Klotho accelerated gastric ulcer healing. (Study 2) We investigated the expression and role of TLR9 in H. pylori-induced gastritis in mice. Our findings suggest that TLR9 signaling plays important roles in the suppression of H. pylori-induced gastric mucosal inflammation in the early phase via downregulation of TNF-alpha modulated by IFN-alpha1. (Study 3) Expression of mRNA for Klotho was downregulated in Hp-infected mice compared uninfected mice, suggesting the promotion of atrophy and carcinogenesis of the stomach .

Research Products

• [Journal Article] 胃潰瘍治癒過程におけるアンチエイジング分子Klothoの発現動態と胃潰瘍治癒に及ぼす影響 (2013)
  • Author(s): 谷川徹也, 渡辺俊雄, 灘谷祐二, 大谷恒史, 十河光栄, 山上博一, 斯波将次, 渡辺憲治, 富永和作, 藤原靖弘, 荒川哲男
  • Journal Title: 潰瘍 Volume: 40巻 Pages: 64-68
  • NAID: 10031177503
• [Journal Article] 胃潰瘍治癒過程におけるアンチエイジング分子Klothoの発現動態と胃潰瘍治癒に及ぼす影響 (2013)
  • Author(s): 谷川 徹也, 渡辺 俊雄, 灘谷 祐二, 大谷 恒史, 十河 光栄, 山上 博一, 斯波 将次, 渡辺 憲治, 富永 和作, 藤原 靖弘, 荒川 哲男
  • Journal Title: 潰瘍 Volume: 40 Pages: 64-68
  • NAID: 10031177503
• [Journal Article] Toll-like receptor 9 signaling has anti-inflammatory effects on the early phase of Helicobacter pylori-induced gastritis. (2012)
  • Author(s): Otani K, Tanigawa T, Watanabe T, Nadatani Y, Sogawa M, Yamagami H, Shiba M, Watanabe K, Tominaga K, Fujiwara Y, Arakawa T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 426 Issue: 3 Pages: 342-9
  • DOI: 10.1016/j.bbrc.2012.08.080
  • Peer Reviewed
• [Journal Article] Toll-like receptor 9シグナルはHelicobacter pylori誘発胃炎の初期過程において抗炎症効果を有する (2012)
  • Author(s): 谷川徹也, 大谷恒史, 渡辺俊雄, 灘谷祐二, 岡崎博俊, 町田浩久, 山上博一, 渡辺憲治, 富永和作, 藤原靖弘, 荒川哲男
  • Journal Title: 消化器と免疫 Volume: 48 Pages: 97-100
• [Journal Article] Klotho, an Aging Suppressor, and Fibroblast Growth Factor 23 is Involved in Gastric Ulcer Healing (2012)
  • Author(s): Tetsuya Tanigawa, Toshio Watanabe, Yuji Nadatani, Koji Otani, Hirohisa Machida, Hirotoshi Okazaki, Hirokazu Yamagami, Kenji Watanabe, Kazunari Tominaga, Yasuhiro Fujiwara, Tetsuo Arakawa
  • Journal Title: Gastroenterology Volume: 142;Supple1
• [Presentation] Anti-inflammatory effect of Toll-like receptor 9 signaling on Helicobacter pylori-induced gastritis (2014)
  • Author(s): Tetsuya Tanigawa, ほか
  • Organizer: 17th Biennial Meeting of Society for Free Radical research International (SFRRI 2014)
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-03-24
• [Presentation] Helicobacter pylori誘発胃炎におけるToll-like receptor 9の意義 (2014)
  • Author(s): 大谷恒史, 谷川徹也, ほか
  • Organizer: 第20回日本ヘリコバクター学会学術集会
  • Place of Presentation: 東京ステーションコンファレンス
• [Presentation] Anti-inflammatory effect of Toll-like receptor 9 signaling on Helicobacter pylori-induced gastritis (2014)
  • Author(s): Tanigawa T, Otani K, Watanabe T, Nadatani Y, Sogawa M, Yamagami H, Shiba M, Watanabe K, Tominaga K, Fujiwara Y, Arakawa T.
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International (SFRRI 2014)
  • Place of Presentation: 京都国際会館
• [Presentation] 胃潰瘍治癒過程におけるアンチエイジング分子klothoの発現動態と潰瘍治癒促進作用 (2012)
  • Author(s): 谷川徹也, ほか
  • Organizer: 第8回日本消化管学会総会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2012-02-12
• [Presentation] 胃潰瘍治癒過程におけるアンチエイジング分子Klothoの発現動態と潰瘍治癒に及ぼす影響 (2012)
  • Author(s): 谷川徹也, ほか
  • Organizer: 日本潰瘍学会学術集会
  • Place of Presentation: 京王プラザ新宿(東京)
• [Presentation] Klotho, an aging suppressor, and fibroblast growth factor 23 is involved in gastric ulcer healing (2012)
  • Author(s): Tetsuya Tanigawa, ほか
  • Organizer: DDW 2012
  • Place of Presentation: San Diego Convention Center (San Diego, United States of America)
• [Presentation] 胃潰瘍治癒過程におけるアンチエイジング分子Klothoの発現動態と潰瘍治癒に及ぼす影響 (2012)
  • Author(s): 谷川 徹也、渡辺 俊雄、灘谷 祐二、大谷 恒史、十河 光栄、山上 博一、斯波 将次、渡辺 憲治、富永 和作、藤原 靖弘、荒川 哲男
  • Organizer: 日本潰瘍学会学術集会
  • Place of Presentation: 京王プラザ新宿（東京）
• [Presentation] Klotho, an aging suppressor, and fibroblast growth factor 23 is involved in gastric ulcer healing (2012)
  • Author(s): Tetsuya Tanigawa, Toshio Watanabe, Yuji Nadatani, Koji Otani, Hirohisa Machida, Hirotoshi Okazaki, Hirokazu Yamagami, Kenji Watanabe, Kazunari Tominaga, Yasuhiro Fujiwara, Tetsuo Arakawa
  • Organizer: DDW 2012
  • Place of Presentation: San Diego Convention Center (San Diego, United States of America)