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Elucidation of the molecular mechanism and functions of mucus-glycoprotein in intestinal drug absorption.

Research Project

Project/Area Number 17K15522
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

Kishimoto Hisanao  東京薬科大学, 薬学部, 助教 (80723600)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords非攪拌水層 / 膜結合型mucin / MUC1 / 腸管吸収 / 粘液層 / mucin / 薬物吸収 / 抗がん剤 / 相互作用 / 薬学 / 生体分子 / 蛋白質
Outline of Final Research Achievements

The unstirred water layer (UWL) permeation is suggested to be a rate-limiting step in the intestinal absorption of hydrophobic drugs. The major glycoprotein components of the UWL are mucins, which classified into two structural types: secretory and membrane-bound mucins. Each membrane-bound mucin has a large extracellular domain, which is heavily glycosylated, their intestinal expression in gastrointestinal tract may affect intestinal drug absorption. However, there have been no reports that describe the contribution of mucins to intestinal drug absorption at the molecular level. In this research project, we focused on typical membrane-bound type mucins (MUC1 and MUC13) expressed in gastrointestinal tract, and demonstrated that MUC1 could be limit the permeation of hydrophobic drugs. Furthermore, we found that the effect of mucin on the membrane permeation process may be different from molecular types, based on the molecular size of extracellular domain.

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまでの薬物吸収理論において粘液層全体への考察に留まっていた脂溶性薬物と粘液層との関係性について分子論的な評価・考察を可能にした。本研究で得られた成果は、医薬品開発における腸管吸収の適正な評価法を確立する上での有益な情報を与えるものと考えられ、ヒト腸管における薬物吸収の高精度予測を可能にするための基盤情報を提供し、医薬品開発の効率化・臨床開発の成功確率向上にも貢献するものと期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Presentation] 抗がん剤の細胞膜透過性に対するmucin分子の抑制効果2019

    • Author(s)
      宮崎歌織、岸本久直、藤澤弘、白坂善之、井上勝央
    • Organizer
      日本薬学会 第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 薬物の細胞膜透過過程における粘液層構成タンパク質MUC1の影響2018

    • Author(s)
      宮崎歌織、岸本久直、大森萌子、白坂善之、井上勝央
    • Organizer
      日本薬剤学会 第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脂溶性薬物の腸管吸収における薬物-粘液間相互作用の評価2018

    • Author(s)
      田野文音、岸本久直、宮崎歌織、大森萌子、白坂善之、井上勝央
    • Organizer
      日本薬剤学会 第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The relation between regional distribution of mucin molecules and intestinal drug absorption in rat small intestine2018

    • Author(s)
      Kaori Miyazaki, Hisanao Kishimoto, Yoshiyuki Shirasaka, Katsuhisa Inoue
    • Organizer
      The 2nd Workshop for Japan-Korea Young Scientists on Pharmaceutics
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MUC1 is involved in the membrane permeation of hydrophobic drugs2018

    • Author(s)
      Kaori Miyazaki, Hisanao Kishimoto, Hiroshi Fujisawa, Yoshiyuki Shirasaka, Katsuhisa Inoue
    • Organizer
      第33回日本薬物動態学会/第22回MDOシンポジウム合同国際学会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of the transcellular transport of hydrophobic drugs in MUC1-knockout MDCKII cells2018

    • Author(s)
      Hisanao Kishimoto, Kaori Miyazaki, Yoshiyuki Shirasaka, Katsuhisa Inoue
    • Organizer
      第33回日本薬物動態学会/第22回MDOシンポジウム合同国際学会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 薬物の生体膜透過機構における膜結合型mucinの影響2018

    • Author(s)
      宮崎歌織、岸本久直、白坂善之、井上勝央
    • Organizer
      第40回 生体膜と薬物の相互作用シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 内因性MUC1ノックアウトMDCKII細胞を用いた脂溶性薬物の経細胞輸送評価2018

    • Author(s)
      岸本久直、宮崎歌織、白坂善之、井上勝央
    • Organizer
      第40回 生体膜と薬物の相互作用シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 薬物の腸管吸収における粘液層構成タンパク質mucinの影響2018

    • Author(s)
      岸本久直
    • Organizer
      第3回トランスポーター研究会関東部会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Effect of mucus layer on the transcellular absorption of lipophilic drugs in rat small intestine2018

    • Author(s)
      Hisanao Kishimoto, Kaori Miyazaki, Yoshiyuki Shirasaka, Katsuhisa Inoue
    • Organizer
      Experimental Biology 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脂溶性薬物の腸管膜透過性に及ぼす腸管粘液の影響及びmucin発現解析2017

    • Author(s)
      宮崎歌織、岸本久直、村谷美穂、田野文音、白坂善之、井上勝央
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 薬物の経粘膜透過に与える粘液層の影響とその分子メカニズム解明に向けたアプローチ2017

    • Author(s)
      岸本久直、宮崎歌織、村谷美穂、白坂善之、井上勝央
    • Organizer
      第39回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Regional distribution of mucin molecules in rat small intestine2017

    • Author(s)
      宮崎歌織、岸本久直、白坂善之、井上勝央
    • Organizer
      日本薬物動態学会 第32回年会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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