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Analysis of pleiotropic property of thrombomodulin and development of therapeutic strategy using thrombomodulin in transplantation

Research Project

Project/Area Number 25461942
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionAichi Medical University (2015)
Nagoya University (2013-2014)

Principal Investigator

MIWA YUKO  愛知医科大学, 医学部, 寄附講座 助教 (90572941)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI TAKAAKI  愛知医科大学, 医学部 外科学講座(腎移植外科), 教授 (70314010)
IWASAKI KENTA  愛知医科大学, 医学部 腎疾患・移植免疫学寄附講座, 准教授 (10508881)
Co-Investigator(Renkei-kenkyūsha) ONISHI AKIRA  日本大学, 生物資源科学部, 教授 (30414890)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords移植・再生医療 / 凝固系制御 / 異種移植 / 移植・再生医療
Outline of Final Research Achievements

Thrombomodulin (TM) is a vascular endothelial cell receptor that functions as a cofactor for activated protein C (APC). From the viewpoint of coagulation control using TM in transplantation, two strategy including (i) administration of recombinant soluble thrombomodulin (S-hTM), which has been approved for the treatment of sepsis-induced DIC, and (ii) upregulation of membrane-bound TM (MB-hTM) expression in endothelial cells would be proposed. As a result, S-hTM had more potent capacity of APC production and inhibitory effect on thrombin generation than MB-hTM. In contrast, MB-hTM suppressed the expression of inflammatory factor in endothelial cells. It was speculated that S-hTM treatment would be of assistance during high-risk periods for excessive thrombin formation (e.g., ischemia reperfusion injury or severe infection/rejection). Considering the properties of MB-hTM exhibiting anti-inflammatory function, might be required to long-term stabilization of graft endothelial cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (22 results)

All 2016 2015 2014 2013 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Journal Article] Functional Difference between Membrane-Bound and Soluble Human Thrombomodulin.2015

    • Author(s)
      Miwa Y, Yazaki S, Iwamoto M, Suzuki S, Iwasaki K, Haneda M, Yamamoto K, Maruyama S, Onishi A, Kobayashi T.
    • Journal Title

      Transplantation

      Volume: 99 Issue: 4 Pages: 702-709

    • DOI

      10.1097/tp.0000000000000571

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Comparative analysis of drug action on B-cell proliferation and differentiation for mycophenolic acid, everolimus, and prednisolone.2014

    • Author(s)
      Haneda M, Owaki M, Kuzuya T, Iwasaki K, Miwa Y, Kobayashi T.
    • Journal Title

      Transplantation.

      Volume: 97 Issue: 11 Pages: 405-412

    • DOI

      10.1097/01.tp.0000441826.70687.f6

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical relevance of post-transplant pharmacodynamic analysis of cyclosporine in renal transplantation.2014

    • Author(s)
      Kurata Y, Kuzuya T, Miwa Y, Iwasaki K, Haneda M, Amioka K, Yamada K, Watarai Y, Katayama A, Uchida K, Kobayashi K
    • Journal Title

      International Immunopharmacology

      Volume: 22 Issue: 2 Pages: 384-391

    • DOI

      10.1016/j.intimp.2014.07.022

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] AMP-activated protein kinase as a promoting factor, but complement and thrombin as limiting factors for acquisition of cytoprotection: implications for induction of accommodation.2013

    • Author(s)
      Iwasaki K, Miwa Y, Haneda M, Kuzuya T, Ogawa H, Onishi A, Kobayashi T.
    • Journal Title

      Transpl Int.

      Volume: 26 Issue: 11 Pages: 1138-1148

    • DOI

      10.1111/tri.12186

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト型Endothelial protein C receptor(hEPCR)とthrombomodulin(hTM)の共発現によるブタ内皮細胞における炎症反応制御の比較検討2016

    • Author(s)
      三輪祐子、岩﨑研太、鈴木俊一、岩元正樹、大西彰、小林孝彰
    • Organizer
      第18回日本異種移植研究会
    • Place of Presentation
      長崎市 長崎大学医学部
    • Year and Date
      2016-02-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] Study of proper expression level of human thrombomodulin in pig endothelial cell with effective anti coagulant activity and no bleeding tendency.2015

    • Author(s)
      Miwa Y, Iwasaki K, Suzuki S, Iwamoto M, Onishi A, Kobayashi T
    • Organizer
      IPITA-IXA-CTS 2015 Joint Congress
    • Place of Presentation
      Melbourne,Australia
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ABO不適合腎移植におけるリスク因子の総合解析:レシピエント抗A/Bサブクラス、C1q,ドナーA/B抗原発現量の評価2015

    • Author(s)
      三輪祐子、山本貴之、岡田学、岩﨑研太、渡井至彦、武田朝美、丸山彰一、小林孝彰
    • Organizer
      第51回日本移植学会総会
    • Place of Presentation
      熊本市 ホテル日航熊本
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト型トロンボモジュリンを発現するcloned pig 作成における適正な発現レベルの検討2015

    • Author(s)
      三輪祐子、岩﨑研太、鈴木俊一、岩元正樹、大西彰、小林孝彰
    • Organizer
      第51回日本移植学会総会
    • Place of Presentation
      熊本市 ホテル日航熊本
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ブタ血管内皮細胞における適正なヒト型トロンボモジュリンの発現レベルの検討2015

    • Author(s)
      三輪祐子、岩﨑研太、羽根田正隆、鈴木俊一、岩元正樹、大西彰、小林孝彰
    • Organizer
      第17回 日本異種移植研究会
    • Place of Presentation
      栃木県下野市 自治医科大学
    • Year and Date
      2015-03-14
    • Related Report
      2014 Research-status Report
  • [Presentation] 異種移植におけるヒト型トロンボモジュリンの有効性2015

    • Author(s)
      三輪祐子、岩﨑研太、羽根田正隆、鈴木俊一、岩元正樹、大西彰、小林孝彰
    • Organizer
      第26回東海北陸腎不全治療研究会
    • Place of Presentation
      愛知県名古屋市 コンベンションルームAP名古屋
    • Year and Date
      2015-02-28
    • Related Report
      2014 Research-status Report
  • [Presentation] Can human thrombomodulin make a major contribution to xenograft survival ?2014

    • Author(s)
      Takaaki Kobayashi.
    • Organizer
      3rd Symposium of East Asia Xenotransplantation Association,
    • Place of Presentation
      Changsha (China)
    • Year and Date
      2014-10-16
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ABO血液型不適合移植はGraft Accommodationを促進するか?抗HLA抗体による慢性抗体関連型拒絶反応に与える影響2014

    • Author(s)
      岩﨑研太、三輪祐子、羽根田正隆、片山昭男、鳴海俊治、渡井至彦、武田朝美、小林孝彰
    • Organizer
      第50回 日本移植学会総会
    • Place of Presentation
      東京都新宿区 京王プラザホテル
    • Year and Date
      2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] ABO不適合腎移植におけるリスク因子の総合解析:IgM, IgGサブクラスおよびドナー抗原量の解析2014

    • Author(s)
      三輪祐子、山本貴之、岩﨑研太、羽根田正隆、後藤憲彦、渡井至彦、武田朝美、両角國男、 丸山彰一、小林孝彰
    • Organizer
      第50回日本移植学会総会
    • Place of Presentation
      東京都新宿区 京王プラザホテル
    • Year and Date
      2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 抗凝固因子thrombomodulinに着目した異種移植における凝固異常の調節2014

    • Author(s)
      三輪祐子、岩﨑研太、羽根田正隆、鈴木俊一、岩元正樹、大西彰、小林孝彰
    • Organizer
      第50回日本移植学会総会
    • Place of Presentation
      東京都新宿区 京王プラザホテル
    • Year and Date
      2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Everolimusの内皮細胞への影響に関する検討2014

    • Author(s)
      堀見孔星、三輪祐子、岩﨑研太、小林孝彰、打田和治
    • Organizer
      第50回 日本移植学会総会
    • Place of Presentation
      東京都新宿区 京王プラザホテル
    • Year and Date
      2014-09-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of therapeutic interventions using anticoagulant factor thrombomodulin in organ transplantation2013

    • Author(s)
      Yuko Miwa, Kenta Iwasaki, Masataka Haneda, Masaki Iwamoto, Akira Onishi, Takaaki Kobayashi
    • Organizer
      The 13th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Kyoto International Conference Center (Kyoto)
    • Related Report
      2013 Research-status Report
  • [Presentation] 液性拒絶反応における血管内皮細胞の役割と凝固制御の役割2013

    • Author(s)
      三輪祐子、山本貴之、岩崎研太、羽根田正隆、後藤憲彦、渡井至彦、武田朝美、丸山彰一、小林孝彰
    • Organizer
      第49回日本移植学会総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Control of procoagulant state using anticoagulant factor thrombomodulin in xenotransplantation2013

    • Author(s)
      Yuko Miwa, Kenta Iwasaki, Masataka Haneda, Masaki Iwamoto, Akira Onishi, Takaaki Kobayashi
    • Organizer
      The 12th Congress International Xenotransplantation Association
    • Place of Presentation
      Osaka International Convention Center (Osaka)
    • Related Report
      2013 Research-status Report
  • [Presentation] 移植医療における抗凝固因子トロンボモジュリンを用いた治療戦略

    • Author(s)
      三輪祐子、岩崎研太、羽根田正隆、岩元正樹、大西彰、小林孝彰
    • Organizer
      第16回日本異種移植研究会
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Related Report
      2013 Research-status Report
  • [Remarks] 愛知医科大学医学部腎疾患・移植免疫学寄附講座ホームページ

    • URL

      http://www.aichi-med-u.ac.jp/su06/su0607/su060704/1197954_1443.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 名古屋大学大学院医学研究科 移植免疫学寄附講座

    • URL

      http://www.med.nagoya-u.ac.jp/tx-immunology

    • Related Report
      2014 Research-status Report
  • [Remarks] 名古屋大学大学院医学研究科 移植免疫学寄附講座

    • URL

      http://www.med.nagoya-u.ac.jp/tx-immunology/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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