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Micro RNA-mediated expressional regulation of transporters

Research Project

Project/Area Number 16K15158
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionKanazawa University

Principal Investigator

Ikumi Tamai  金沢大学, 薬学系, 教授 (20155237)

Co-Investigator(Kenkyū-buntansha) 中西 猛夫  金沢大学, 薬学系, 准教授 (30541742)
中島 美紀  金沢大学, 薬学系, 教授 (70266162)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsトランスポーター / OATP / マイクロRNA / ナノ粒子 / 薬食相互作用 / 薬物間相互作用 / 個体間変動 / 食品 / 消化管 / 輸送体 / 筋肉 / 筋毒性 / 発現調節 / 予測マーカー / 薬物動態
Outline of Final Research Achievements

To understand the mechanisms for altered drug absorption and disposition by co-administered drugs and foods, we studied possible involvement of micro RNA (miRNA) on the expressional regulation of drug transporter OATPs. (1) OTAP2B1, which is expressed both in liver and intestine, was found to be regulated by specific miRNA by in vitro experiments. (2) Statins are very good substrates of OATPs and they have possibility to cause myopathy as side effect. We succeeded to suggest several miRNA that can be used for diagnosis of myopathy. (3) As the mechanism of drug-food interaction, it was demonstrated that apple-derived nanoparticles include many miRNAs and they affect expression of OATP2B1, suggesting that food-derived miRNAs could regulate expression of OATPs, (4) Transporters responsible for intestinal absorption of anti-cancer nucleoside analogue were identified and further studies to demonstrate the mechanisms to regulate their expression, including miRNA should be conducted.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results)

  • [Journal Article] Contribution of equilibrative nucleoside transporters(s) to intestinal basolateral and apical transport of anticancer trifluridine2018

    • Author(s)
      Takahashi K, Yoshisue K, Chiba M, Nakanishi T, Tamai I
    • Journal Title

      Biopharmaceutics & Drug Disposition

      Volume: 39 Issue: 1 Pages: 38-46

    • DOI

      10.1002/bdd.2110

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Revisiting the role of gut wall in the face of orally administered drugs: Why now and to what effect?2017

    • Author(s)
      Rostami-Hodjegan A, Tamai I, Pang S.
    • Journal Title

      Biopharmaceutics & Drug Disposition

      Volume: 38 Issue: 2 Pages: 87-93

    • DOI

      10.1002/bdd.2071

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association of miR-145 with statin-induced skeletal muscle toxicity in human rhabdomyosarcoma RD cells.2017

    • Author(s)
      Saito S, Nakanishi T, Shirasaki Y, Nakajima M, Tamai I.
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Regulatory Effect of Fruit-derived Nanoparticle on Intestinal Transporters2018

    • Author(s)
      Daichi Fujita, Toshiki Arai, Yuma Shirasaki, Yui Iwamoto, Hisakazu Komori, Takeo Nakanishi, Ikumi Tamai
    • Organizer
      Experimental Biology 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Drug-Drug and Drug-Food Interaction on Transporters2018

    • Author(s)
      Ikumi Tamai
    • Organizer
      CPSA Shanghai 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanism and Impact of Drug-Drug and Drug-Food Interactions on Transporters2018

    • Author(s)
      Ikumi Tamai
    • Organizer
      3rd Drug Transporter International Forum
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 薬物吸収とトランスポーター2018

    • Author(s)
      玉井郁巳
    • Organizer
      日本TDM学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 果物由来ナノ粒子が及ぼす小腸輸送体への影響2017

    • Author(s)
      荒井俊樹、白崎佑磨、小森久和、中西猛夫、玉井郁巳
    • Organizer
      日本薬学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Food-Drug and Drug-Drug Interactions2017

    • Author(s)
      Ikumi Tamai
    • Organizer
      Meet the Expert, Transporter Conference, 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Effect of Fruit-derived nanoparticle on intestinal transporters2017

    • Author(s)
      Toshiki Arai, Yuma Shirasaki, Daichi Fujita, Takeo Nakanishi, Ikumi Tamai
    • Organizer
      第32回日本薬物動態学会年会
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-03-29  

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