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Regulation of intestinal function via microRNA from fruit-derived microvesicles

Research Project

Project/Area Number 20K21474
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionKanazawa University

Principal Investigator

Tamai Ikumi  金沢大学, 薬学系, 教授 (20155237)

Co-Investigator(Kenkyū-buntansha) 中島 美紀  金沢大学, ナノ生命科学研究所, 教授 (70266162)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords食品作用 / 食品由来微粒子 / マイクロRNA / トランスポーター / 発現調節 / 栄養素 / 食品 / 食品由来マイクロベシクル / 食品由来高分子成分 / OATP2B1 / リンゴ / ASBT / ナノ粒子 / 消化管機能
Outline of Research at the Start

果物などの食品には細胞外ナノ粒子(eNP)が存在し、内包物を安定に保ちつつ細胞内へ移行させ、内包高分子をヒト組織に作用させることが示唆され始めた。本研究では、代表者が培養細胞において見出した「リンゴ由来eNPによる小腸上皮輸送体OATP2B1タンパク質の発現量低下」という知見に基づいた「eNPに内包される高分子化合物(マイクロRNA)がヒトの消化管機能を直接的に調節する」という仮説を実証する。本研成果は、eNPによってマイクロRNAに限らず含有高分子が直接消化管機能を調節するという新規食品機能の概念と、高分子化合物の医療・健康への利用という新しいDDS手法の提唱をめざす。

Outline of Final Research Achievements

Nutrients in food affect human (host) as small molecules such as metals, flavonoids and amino acids derived as digestive products of proteins, which are large molecules. However, recently it is demonstrated that food include many micro-vesicles and they contain variable large molecules such as food-derived microRNA. Accordingly, it is possible that large molecules of food may directly affect host function, though currently only small molecules are considered to cause physiological effect on host. In this study, we found that apple-derived micro-vesicles contain variable apple-derived microRNAs and they are delivered to intestinal epithelial cells in the form of micro-vesicles. Then, contained microRNAs directly regulate expression of several transporter proteins. Accordingly, by considering such micro-vesicles in food, we need to add direct effect of food-contained large molecules as food function in addition to currently well recognized nutrients definition as small molecules.

Academic Significance and Societal Importance of the Research Achievements

タンパク質など食品由来高分子がヒトに作用する場合は消化産物であるアミノ酸のような低分子である。その他、単糖、金属、フラボノイドなどいずれも直接作用するのは低分子であるというのが現在の栄養学である。一方本研究では、食品中には微粒子が含まれ、それはマイクロRNAなど食品由来高分子を含有することを示した。さらに微粒子はマイクロRNAなど高分子を安定に保ち、小腸上皮細胞内に移行させ、内包したマイクロRNAが直接的に小腸細胞のタンパク質機能を調節すること見出した。即ち、食品由来高分子が直接栄養素として働くことを示す。従って、栄養素の定義として食品由来高分子も考慮する必要のあることを示す意義がある。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2022 2021 2020

All Journal Article (5 results) (of which Peer Reviewed: 2 results) Presentation (4 results)

  • [Journal Article] 食品成分と薬物の相互作用2022

    • Author(s)
      玉井郁巳、朱秋楠
    • Journal Title

      実験医学増刊

      Volume: 40-7 Pages: 70-77

    • Related Report
      2021 Annual Research Report
  • [Journal Article] MicroRNAs in apple-derived nanoparticles modulate intestinal expression of OATP2B1/SLCO2B1 in humans.2021

    • Author(s)
      Komori H, Fujita D, Shirasaki Y, Zhu Q, Iwamoto Y, Nakanishi T, Nakajima N, Tamai I.
    • Journal Title

      Drug Meatbolism and Disposition

      Volume: 49 Issue: 9 Pages: 803-809

    • DOI

      10.1124/dmd.121.000380

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel fluorescence-based method to evaluate ileal apical sodium-dependent bile acid transporter ASBT.2021

    • Author(s)
      Zhu Q, Komori H, Imamura R, Tamai I.
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 110 Issue: 3 Pages: 1392-1400

    • DOI

      10.1016/j.xphs.2020.11.030

    • Related Report
      2020 Research-status Report
  • [Journal Article] Uptake pathway of apple-derived nanoparticle by intestinal cells to deliver its cargo.2021

    • Author(s)
      Arai M, Komori H, Fujita D, Tamai I
    • Journal Title

      Pharmaceutical Research

      Volume: 38 Issue: 3 Pages: 523-530

    • DOI

      10.1007/s11095-021-03018-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Post-transcriptional regulation of OATP2B1 transporter by a microRNA, miR-24.2020

    • Author(s)
      Liu W, Nakano M, Nakanishi T, Nakajima M, Tamai I.
    • Journal Title

      Drug Metabbolism and Pharmacokinetics

      Volume: 35 Issue: 6 Pages: 515-521

    • DOI

      10.1016/j.dmpk.2020.07.007

    • NAID

      50014656610

    • Related Report
      2020 Research-status Report
  • [Presentation] Constipation-relieving effect of apple due to down-regulation of ASBT2021

    • Author(s)
      Qiunan Zhu, Takehiro Okaguchi, Ryusuke Iwai, Hisakazu Komori, Yoshiyuki Shirasaka, Ikumi Tamai
    • Organizer
      日本薬物動態学会第36回年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Down-regulation of OATP2B1/SLCO2B1 Expression by MicroRNAs in Apple-derived Nanoparticles2021

    • Author(s)
      Hisakazu Komori, Daichi Fujita, Yuma Shirasaki, Mayumi Arai,Qiunan Zhu, Ikumi Tamai
    • Organizer
      日本薬物動態学会第36回年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] リンゴ由来ナノ粒子中の高分子成分による回腸胆汁酸輸送体ASBTの発現調節2021

    • Author(s)
      臼井紳也、小森久和、岩本結、稲永上輝、白坂善之、玉井郁巳
    • Organizer
      第133回日本薬学会北陸支部
    • Related Report
      2021 Annual Research Report
  • [Presentation] A novel fluorescence-based method to evaluate the ileal apical sodium-dependent bile acid transporter ASBT2020

    • Author(s)
      Qiunan Zhu, Hisakazu Komori, Rikako Imamura, Ikumi Tamai
    • Organizer
      トランスポーター研究会、関東
    • Related Report
      2020 Research-status Report

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Published: 2020-08-03   Modified: 2023-01-30  

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