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Development of disease-specific treatments based on pathophysiology of polycystic kidney disease with a focus on tissue transglutaminase

Research Project

Project/Area Number 20K08162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionUniversity of the Ryukyus

Principal Investigator

Nakanishi Koichi  琉球大学, 医学(系)研究科(研究院), 教授 (50336880)

Co-Investigator(Kenkyū-buntansha) 島 友子  和歌山県立医科大学, 医学部, 講師 (60433364)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords多発性嚢胞腎 / 上皮間葉移行 / 増殖 / 分泌 / 細胞外基質 / 組織トランスグルタミナーゼ / miRNA / 多発性のう胞腎 / 疾患特異的治療
Outline of Research at the Start

多発性嚢胞腎(polycystic kidney disease、PKD)は、慢性腎不全の主要な原因の一つである。常染色体優性と常染色体劣性があり、臨床上の差違にもかかわらず共通の基本的病態生理が存在する。
本研究では、PKDの複数の基本的病態生理における組織トランスグルタミナーゼの関与とその機序を解明し、それらを修飾することによる病態生理に基づいた疾患特異的治療開発のための基礎的知見の獲得、およびそのヒトへの応用のためのモデル動物を用いた治療研究による効果の確認を目指す。

Outline of Final Research Achievements

The purpose of this study is to elucidate the involvement of tissue transglutaminase in multiple basic pathophysiologies of polycystic kidney disease (PKD) and its mechanisms, to obtain basic knowledge for the development of pathophysiology-based disease-specific therapies by modifying them, and to confirm their efficacy in humans by using animal models for their application. The research is to confirm the efficacy of the treatment by using model animals for its application to humans.
Until R3, we have been analyzing the pathophysiology of ARPKD by focusing on the relationship between tissue transglutaminase expression in cultured PKD cell lines and ARPKD animal model-derived tissues and the miRNA data accumulated so far in the ARPKD model.
In R4, we are further analyzing the data by real-time PCR, Western blotting, and immunostaining.

Academic Significance and Societal Importance of the Research Achievements

多発性嚢胞腎の複数の基本的病態生理における組織トランスグルタミナーゼの関与とその機序が解明され、それらを修飾することによる病態生理に基づいた疾患特異的治療開発のための基礎的知見が獲得され、そのヒトへの応用のためのモデル動物を用いた治療研究による効果が確認されれば、新しい治療法の開発に繋がる可能性があり、医学・医療に貢献する。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (12 results)

All 2022 2021 2020

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] 遺伝性腎疾患2022

    • Author(s)
      中西浩一
    • Journal Title

      周産期医学

      Volume: 52 Pages: 747-750

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 常染色体潜性多発性嚢胞腎の基礎と臨床―up date2022

    • Author(s)
      中西浩一
    • Journal Title

      医学と薬学

      Volume: 79 Pages: 927-934

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ARPKDの病因と病態2022

    • Author(s)
      中西浩一
    • Journal Title

      腎と透析

      Volume: 93 Pages: 489-492

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 多発性嚢胞腎と移行期医療2021

    • Author(s)
      中西浩一
    • Journal Title

      腎臓内科

      Volume: 14 Pages: 184-191

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] ARPKD 1)病態生理と治療2021

    • Author(s)
      中西浩一
    • Journal Title

      腎臓内科

      Volume: 14 Pages: 560-566

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 遺伝学的に診断できた常染色体劣性多発性嚢胞腎の遺伝型と臨床像2020

    • Author(s)
      森貞直哉, 野津寛大, 中西浩一, 飯島一誠
    • Journal Title

      発達腎研究会誌

      Volume: 28 Pages: 33-35

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] 多発性嚢胞腎2020

    • Author(s)
      中西浩一
    • Journal Title

      小児科臨床

      Volume: 73 Pages: 782-785

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] 多発性嚢胞腎-ARとADを含めて-2020

    • Author(s)
      中西浩一
    • Journal Title

      腎と透析

      Volume: 89 Pages: 856-861

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Two male relatives with OFD1 mutations.2021

    • Author(s)
      Wada T, Shima Y, Tanaka Y, Mukaiyama H, Morisada N, Nozu K, Iijima K, Nakanishi K.
    • Organizer
      The 18th Japan-Korea-China pediatric Nephrology Seminar 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] A case of Potter sequence with WT1 gene mutation.2021

    • Author(s)
      Shimabukuro W, Yoshino M, Takeichi M, Omura J, Yokota C, Yamamoto J, Takahashi Y, Nozu K, Morisada N, Iijima K, Nakanishi K.
    • Organizer
      The 14th Asian Congress of Pediatric Nephrology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] ARPKD―今できること,そして今後の課題―2021

    • Author(s)
      中西浩一
    • Organizer
      第64回日本腎臓学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Book] エビデンスに基づく多発性嚢胞腎PKD診療ガイドライン20202020

    • Author(s)
      成田一衛、他
    • Total Pages
      92
    • Publisher
      東京医学社
    • ISBN
      9784885637247
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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