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the role of biometal in the intestinal environment

Research Project

Project/Area Number 21H02897
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Oshima Shigeru  東京医科歯科大学, 統合研究機構, 教授 (50376787)

Co-Investigator(Kenkyū-buntansha) 宇尾 基弘  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (20242042)
岡本 隆一  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50451935)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2022: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2021: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywordsクローン病 / A20 / 腸炎 / ユビキチン / ニッケル / 炎症性腸疾患 / 生命金属 / オートファジー / TNFAIP3 / TNFAIP3/A20
Outline of Research at the Start

従来、食品等から採り込まれた生命金属は必要量のみが吸収され、余剰分は速やかに体外に排除・排泄されるため、消化管疾患発症の要因とは考えられていなかった。しかしながら生活習慣等の変化により多彩な生命金属に暴露する機会や総曝露量が増加したことにより、従来の考え方を転換する必要性が高まっている。このように、「腸内環境における生命金属の役割」の解明と新たな角度からの病態理解を行う研究である。

Outline of Final Research Achievements

We have discovered the deposition of nickel particles in Crohn's disease intestinal tissues. Analysis of human disease samples so far has not shown deposition in non-cancerous parts of colorectal cancer tissues or tissues of ulcerative colitis. Using cell lines, we have elucidated the cellular alterations caused by nickel particles and have also revealed that nickel particles exacerbate intestinal inflammation in mutant mice of the Crohn's disease susceptibility gene A20/TNFAIP3.

Academic Significance and Societal Importance of the Research Achievements

クローン病や潰瘍性大腸炎などの炎症性腸疾患は、日本で急増している原因不明の消化管難病です。これらの病気の発症に直結する決定的な環境因子はまだ特定されていません。今回、これまで全く解析されていなかった生命金属の観点から調査を行い、クローン病の腸管組織にニッケル粒子が沈着していることを発見し、動物モデルで検証しました。健康な人では経口摂取した生命金属は体外に排出されますが、クローン病の遺伝的背景を持つ人(A20/TNFAIP3変異など)では、何らかの理由でニッケル粒子が腸管に蓄積し、炎症に関与するという新しい仮説が提唱され、大きなインパクトを与えています。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (11 results)

All 2024 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Single cell analysis revealed that two distinct, unique CD4+ T cell subsets were increased in the small intestinal intraepithelial lymphocytes of aged mice.2024

    • Author(s)
      Yuki Yonemoto, Yasuhiro Nemoto, Ryo Morikawa, Nana Shibayama, Shigeru Oshima, Takashi Nagaishi, Tomohiro Mizutani, Go Ito, Satoru Fujii, Ryuichi Okamoto.
    • Journal Title

      Frontiers in Immunology.

      Volume: 15 Pages: 1340048-1340048

    • DOI

      10.3389/fimmu.2024.1340048

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel-time resolved reporter mouse reveals spatial and transcriptional heterogeneity during alpha cell differentiation2023

    • Author(s)
      Himuro M, Wakabayashi Y, Taguchi T, Katahira T, Suzuki L, Iida H, Ogihara T, Nishida Y, Sasaki S, Lynn FC, Hiraoka Y, Oshima S, Okamoto R, Fujitani Y, Watada H, Miyatsuka T
    • Journal Title

      Diabetologia

      Volume: 67 Issue: 1 Pages: 156-169

    • DOI

      10.1007/s00125-023-06028-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Apelin expression is downregulated in T cells in a murine model of chronic colitis2023

    • Author(s)
      Yamada D、Kojima Yi、Hosoya A、Suzuki、Watabe T、Inoue T、Tsugawa N、Asakawa T、Yonemoto Y、Onizawa M、Nemoto Y、Oshima S、Shimonaka M、Kuba Ki、Ishida J、Fukamizu A、Penninger JM、Watanabe M、Okamoto R、Nagaishi T
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 647 Pages: 72-79

    • DOI

      10.1016/j.bbrc.2023.01.068

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zranb1-mutant mice display abnormal colonic mucus production and exacerbation of DSS-induced colitis.2022

    • Author(s)
      Tamura A, Ito G, Matsuda H, Nibe-Shirakihara Y, Hiraoka Y, Kitagawa S, Hiraguri Y, Nagata S, Aonuma E, Otsubo K, Nemoto Y, Nagaishi T, Watanabe M, Okamoto R, Oshima S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 628 Pages: 147-154

    • DOI

      10.1016/j.bbrc.2022.08.046

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nickel particles are present in Crohn's disease tissue and exacerbate intestinal inflammation in IBD susceptible mice.2022

    • Author(s)
      Hiroki Matsuda, Yoichi Nibe-Shirakihara, Akiko Tamura, Emi Aonuma, Satoko Arakawa, Kana Otsubo, Yasuhiro Nemoto, Takashi Nagaishi, Kiichiro Tsuchiya, Shigeomi Shimizu, Averil Ma, Mamoru Watanabe, Motohiro Uo, Ryuichi Okamoto, Shigeru Oshima.
    • Journal Title

      Biochemical and Biophysical Research Communications.

      Volume: 592 Pages: 74-80

    • DOI

      10.1016/j.bbrc.2021.12.111

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production.2021

    • Author(s)
      Ai Minamidate, Michio Onizawa, Chikako Saito, Rie Hikichi, Tomoaki Mochimaru, Mai Murakami, Chiharu Sakuma, Takehito Asakawa, Yuichi Hiraoka, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Hiromasa Ohira, Ryuichi Okamoto, Mamoru Watanabe.
    • Journal Title

      Biochemistry and Biophysics Reports.

      Volume: 27 Pages: 101065-101065

    • DOI

      10.1016/j.bbrep.2021.101065

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral administration of D-serine prevents the onset and progression of colitis in mice.2021

    • Author(s)
      Takehito Asakawa, Michio Onizawa, Chikako Saito, Rie Hikichi, Daiki Yamada, Ai Minamidate, Tomoaki Mochimaru, Shun-ichiro Asahara, Yoshiaki Kido, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Hiromasa Ohira, Ryuichi Okamoto, Mamoru Watanabe.
    • Journal Title

      Journal of Gastroenterolog.

      Volume: 56 Issue: 8 Pages: 732-745

    • DOI

      10.1007/s00535-021-01792-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal.2021

    • Author(s)
      Ryo Morikawa, Yasuhiro Nemoto, Yuki Yonemoto, Shohei Tanaka, Yuria Takei, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Kengo Nozaki , Tomohiro Mizutani, Tetsuya Nakamura, Mamoru Watanabe, Ryuichi Okamoto.
    • Journal Title

      Cell Mol Gastroenterol Hepatol.

      Volume: 11 Issue: 5 Pages: 1483-1503

    • DOI

      10.1016/j.jcmgh.2021.01.014

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腸管炎症惹起機構における生命金属の役割2021

    • Author(s)
      大島 茂、松田浩紀、青沼映美、田村皓子、仁部洋一、渡辺守、宇尾基弘、岡本隆一
    • Organizer
      第94回日本生化学学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 生命金属による腸管炎症・惹起機構の解析2021

    • Author(s)
      松田浩紀、青沼映美、田村皓子、仁部洋一、渡辺守、岡本隆一、宇尾基弘、大島 茂.
    • Organizer
      第58回日本消化器免疫学会
    • Related Report
      2021 Annual Research Report
  • [Book] 創薬研究者・アカデミア研究者が知っておくべき最新の免疫学とその応用技術2021

    • Author(s)
      執筆者:101名、技術情報協会
    • Total Pages
      598
    • Publisher
      技術情報協会
    • ISBN
      4861048567
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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