The impact of PAR-1 and S1PR1 regulation for hepatic ischemia reperfusion injury
| Project/Area Number |
16K10569
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Mie University |
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Principal Investigator |
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| Research Collaborator |
ITO Takahiro 三重大学, 医学(系)研究科(研究院) 病態修復医学講座 肝胆膵・移植外科学所属
SHINKAI Toru 三重大学, 医学(系)研究科(研究院) 救命救急・総合集中治療センター, 助教
NOGUCHI Daisuke 三重大学, 医学(系)研究科(研究院) 地域医療支援センター, 助教
HIBI Tamami 三重大学, 医学(系)研究科(研究院) 病態修復医学講座 肝胆膵・移植外科学, 実験助手
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肝虚血再灌流障害 / S1PR1 / PAR-1 / activated protein C / sphingosine-1-phosphate / hepatic IRI / endothelial cell injury / IRI / 活性化プロテインC |
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| Outline of Final Research Achievements |
S1PR1 agonist induces attenuation of hepatic IRI, which might be provided by preventing SEC damage. S1PR1 may be a therapeutic target for the prevention of early sinusoidal injury after hepatic IRI.
Selective PAR-1 antagonist, vorapaxar, attenuates hepatic IRI, and reduces apoptosis notably. SECs, where PAR-1 expressions are mostly found, are one of critical targets of vorapaxar.
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| Academic Significance and Societal Importance of the Research Achievements |
S1PR1とPAR-1の二つの新たなターゲットの創出の可能性が見出され、凝固線溶系バランスが大きく変動している術後早期にも安全に使用出来るだけでなく、手術関連死亡率の改善と手術適応拡大が期待でき、多大な恩恵を与えるものと考えられる。この実験結果で得られる成果の学術的、治療学的意義は非常に大きく、特に末期肝不全患者や、高度進行肝細胞癌および胆管癌患者において、手術適応と安全性の向上を図ることが可能となり、世界的に大きなインパクトを与えるとものと考えられる。
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Report
(4 results)
Research Products
(11 results)
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[Presentation] マウス肝虚血再灌流障害におけるprotease activated receptor-1の抑制による肝保護効果2018
Author(s)
野口大介, 栗山直久, 伊藤貴洋, 早崎碧泉, 飯澤祐介, 藤井武宏, 加藤宏之, 種村彰洋, 村田泰洋, 安積良紀, 岸和田昌之, 水野修吾, 臼井正信, 櫻井洋至, 伊佐地秀司
Organizer
第118回日本外科学会定期学術集会
Related Report
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[Presentation] Selective inhibition of the thrombin receptor protease-activated receptor-1 induces up-regulation of anti-apoptotic protein ERK1/2 against hepatic ischemia-reperfusion injury in mice2018
Author(s)
Daisuke Noguchi, Naohisa Kuriyama, Takahiro Ito, Aoi Hayasaki, Taishiro Takeuchi, Takehiro Fujii, Yusuke Iizawa, Hiroyuki Kato, Akihiro Tanemura, Yasuhiro Murata, Yoshinori Azumi, Masashi Kishiwada, Shugo Mizuno, Masanobu Usui, Hiroyuki Sakurai, Shuji Isaji
Organizer
第30回日本肝胆膵外科学会学術集会
Related Report
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[Presentation] Role of protease activated receptor 1 and sphingosine-1-phospate receptor 1 in mice hepatic ischemia-reperfusion injury for targeting cell signal pathways of activated protein C2017
Author(s)
Takahiro Ito, Naohisa Kuriyama, Hiroyuki Kato, Yusuke Iizawa, Akihiro Tanemura, Yasuhiro Murata, Yoshinori Azumi, Masashi Kishiwada, Shugo Mizuno, Masanobu Usui, Hiroyuki Sakurai, Shuji Isaji
Organizer
2017 American Transplant Congress
Related Report
Int'l Joint Research
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[Presentation] Endothelial sphingosine-1 phosphate receptor 1 mediates protection from early injury after hepatic ischemia-reperfusion injury in a mouse model2017
Author(s)
Takahiro Ito, Naohisa Kuriyama, Hiroyuki Kato, Akitoshi Matsuda, Akihiro Tanemura, Yasuhiro Murata, Yoshinori Azumi, Masashi Kishiwada, Shugo Mizuno, Masanobu Usui, Hiroyuki Sakurai, Shuji Isaji
Organizer
15th Congress of the Asian Society of Transplantation
Related Report
Int'l Joint Research
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