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Role of antioxidative transcription factor Nrf2 in strategies to protect against ischemia-reperfusion injury after lung transplantation

Research Project

Project/Area Number 26462120
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory surgery
Research InstitutionFujita Health University (2016)
Tohoku University (2014-2015)

Principal Investigator

Hoshikawa Yasushi  藤田保健衛生大学, 医学部, 教授 (90333814)

Co-Investigator(Kenkyū-buntansha) 松田 安史  東北大学, 大学病院, 助教 (00455833)
近藤 丘  東北大学, 加齢医学研究所, 教授 (10195901)
野田 雅史  東北大学, 大学病院, 講師 (70400356)
岡田 克典  東北大学, 加齢医学研究所, 教授 (90323104)
Co-Investigator(Renkei-kenkyūsha) TOGO Takeo  東北大学, 加齢医学研究所, 大学院生
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsNrf2活性化剤 / Nrf2標的遺伝子 / アポトーシス / 肺酸素化能 / Nrf2欠損ラット / 肺水腫 / 血中抗酸化力 / 肺移植 / 虚血再灌流肺障害 / 肺胞水分クリアランス / Nrf2 / oltipraz / 肺コンプライアンス
Outline of Final Research Achievements

To test whether Nrf2 protects lungs from ischemia-reperfusion injury after lung transplantation (LTx), wild-type (WT) rats underwent left LTx from Nrf2 knockout (KO) or WT rats, and pulmonary injury and edema were compared. Lung grafts from Nrf2 KO rats showed more pulmonary edema, reduced lung compliance, and less oxygenation when compared with grafts from WT rats. Pretreatment of the recipient rats with Nrf2 activator oltipraz attenuated ischemia-reperfusion-induced lung edema in the grafts from WT rats, but not in the grafts from Nrf2 KO rats. Oltipraz also induced enhanced expression of Nrf2 target genes, NAD(P)H quinone oxidoreductase 1 (NQO1) and glutamate-cysteine ligase modifier subunit (GCLM) and reduced number of TUNEL positive cells in the grafts from WT rats. These results indicate that Nrf2 plays a role in protection against ischemia-reperfusion injury and that Nrf2 activators have a therapeutic potency for the prevention of primary graft dysfunction after LTx.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Invited: 1 results)

  • [Journal Article] 肺移植後虚血・再灌流肺障害予防戦略における抗酸化転写因子Nrf2の役割の解明2017

    • Author(s)
      星川 康
    • Journal Title

      Organ Biology

      Volume: 印刷中

    • NAID

      130006035082

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Medical Consultant System for Improving Lung Transplantation Opportunities and Outcomes in Japan2015

    • Author(s)
      Y. Hoshikawa, Y. Okada, J. Ashikari, Y. Matsuda, H. Niikawa, M. Noda, T. Sado, T. Watanabe, H. Notsuda, F. Chen, M. Inoue, K. Miyoshi, T. Shiraishi, T. Miyazaki, M. Chida, N. Fukushima, T. Kondo
    • Journal Title

      Transplantation Proceedings

      Volume: 47 Pages: 746-750

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 肺移植 -現状と東北大学での経験-2017

    • Author(s)
      星川 康
    • Organizer
      第12回名古屋肺癌外科研究会
    • Place of Presentation
      TKPガーデンシティPREMIUM名古屋駅前
    • Year and Date
      2017-03-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 肺移植後虚血・再灌流肺障害予防戦略における抗酸化転写因子Nrf2の役割の解明2016

    • Author(s)
      星川 康
    • Organizer
      第43回 日本臓器保存生物医学会
    • Place of Presentation
      東京薬科大学
    • Year and Date
      2016-11-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 本邦脳死肺移植173例のprimary graft dysfunction 危険因子解析2015

    • Author(s)
      星川 康、石橋直也、三好健太郎、南 正人、陳 豊史、白石武史、千田雅之、宮崎拓郎、芦刈淳太郎、三友英紀、秋場美紀、渡邊龍秋、新井川弘道、松田安史、佐渡 哲、野田雅史、伊達洋至、古川博之、近藤 丘、岡田克典
    • Organizer
      第42回日本臓器保存生物医学会学術集会
    • Place of Presentation
      いわて県民情報交流センター、岩手県盛岡市
    • Year and Date
      2015-11-14
    • Related Report
      2015 Research-status Report
  • [Presentation] 本邦脳死肺移植173例における術後primary graft dysfunction 発症の危険因子解析2015

    • Author(s)
      星川 康、石橋直也、三好健太郎、南 正人、陳 豊史、白石武史、千田雅之、宮崎拓郎、芦刈淳太郎、三友英紀、秋場美紀、渡邊龍秋、新井川弘道、松田安史、佐渡 哲、野田雅史、伊達洋至、古川博之、近藤 丘、岡田克典
    • Organizer
      第51回日本移植学会
    • Place of Presentation
      ホテル日航熊本、熊本県熊本市
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 肺移植後急性拒絶反応が肺胞水分クリアランスに及ぼす影響2015

    • Author(s)
      三友英紀、野田雅史、渡邉龍秋、野津田泰嗣、松田安史、新井川弘道、桜田晃、星川康、遠藤千顕、岡田克典、近藤丘
    • Organizer
      日本肺および心肺移植研究会
    • Place of Presentation
      東京大学
    • Year and Date
      2015-01-31
    • Related Report
      2014 Research-status Report
  • [Presentation] 肺移植急性拒絶反応における肺胞上皮を介した水分輸送能の推移2014

    • Author(s)
      三友英紀、野田雅史、野津田泰嗣、松田安史、新井川弘道、前田寿美子、佐渡哲、桜田晃、星川康、遠藤千顕、岡田克典、近藤丘
    • Organizer
      日本移植学会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2014-09-12
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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