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Investigation of candidate drugs for pulmonary hypertension associated with congenital diaphragmatic hernia

Research Project

Project/Area Number 17K11505
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionUniversity of Tsukuba

Principal Investigator

Takayasu Hajime  筑波大学, 医学医療系, 准教授 (10359614)

Co-Investigator(Kenkyū-buntansha) 増本 幸二  筑波大学, 医学医療系, 教授 (20343329)
五藤 周  筑波大学, 医学医療系, 講師 (80598889)
瓜田 泰久  筑波大学, 医学医療系, 講師 (90361352)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords先天性横隔膜ヘルニア / ラットモデル / ナイトロフェン / 肺高血圧 / TSP1 / CD47 / 新生児先天性横隔膜ヘルニア / 肺低形成 / エリスロポエチン / Rho阻害剤 / 胎児治療 / 胎児薬物治療
Outline of Final Research Achievements

The authors has already presented that erythropoietin would be a candidate drug for the treatment for pulmonary hypertension associated with congenital diaphragmatic hernia (CDH). However, erythropoietin showed no effect for pulmonary hypertension in this studies. The authors thought that erythropoietin was too big to pass the blood placenta barrier. Then the authors focused on TSP1 and CD47, which were reported to be involved in the mechanism of pulmonary hypertension. The authors found elevated expression of TSP1 and CD47 in CDH model. Therefore, anti CD47 antibody is thought to be another candidate for CDH patients. Because anti CD47 antibody will used clinically near in the future for cancer treatment, anti CD47 antibody is one of the hopeful candidate for treatment of CDH.

Academic Significance and Societal Importance of the Research Achievements

肺高血圧におけるEpoとRhoキナーゼ両方の系に関わる物質で治療につながる経路の物質としてTSP1とCD47に着目した。特に肺高血圧の動物実験や臨床検討でも上昇が報告されていたTSP1は、本CDHモデルにても発現レベルの上昇をmRNAのレベルにおいても蛋白レベルにおいても認めた。TSP1のレセプターであり、肺高血圧の調節にとり重要なNOの上流に位置するCD47についても発現レベルの上昇を認めた。肺高血圧に、両者が強く働いていることが示唆された。また、TSP1の発現調節を行っているRunx3とEgr1の高発現も認め、本CDHモデルにおける肺高血圧の重要なメカニズムと考えられた。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2021 2019

All Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] 先天性横隔膜ヘルニアRatモデルにおけるCD47とTSP1の高発現2021

    • Author(s)
      高安 肇、増本幸二
    • Organizer
      第112回日本小児外科学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Long-term Follow-up in Surgical Newborns: A single institution’s experience2019

    • Author(s)
      Hajime Takayasu, Kouji Masumoto, Kazuki Shirane, Yasunari Tanaka, Tsubasa Aiyoshi, Takato Sasaki, Kentaro Ono, Fumiko Chiba, Chikashi Gotoh, Yasuhisa Urita, Toko Shinkai
    • Organizer
      52nd PAPS Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当院における新生児外科手術症例の長期フォローの状況について2019

    • Author(s)
      高安 肇, 増本 幸二, 田中 保成, 相吉 翼, 佐々木 理人, 小野 健太郎, 千葉 史子, 五藤 周, 瓜田 泰久, 新開 統子
    • Organizer
      第55回日本周産期・新生児医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 当院における新生児外科手術症例の長期フォローの状況について2019

    • Author(s)
      高安 肇, 増本 幸二, 田中 保成, 相吉 翼, 佐々木 理人, 小野 健太郎, 千葉 史子, 五藤 周, 瓜田 泰久, 新開 統子
    • Organizer
      第56回日本小児外科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Long-term Follow-up in Surgical Newborns: A single institution’s experience2019

    • Author(s)
      Hajime Takayasu, Kouji Masumoto, Kazuki Shirane, Yasunari Tanaka, Tsubasa Aiyoshi, Takato Sasaki, Kentaro Ono, Fumiko Chiba, Chikashi Gotoh, Yasuhisa Urita, Toko Shinkai
    • Organizer
      Pacific Association of Pediatric Surgeons 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2024-12-25  

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