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The role of blood coagulation and fibrinolysis system in the oxaliplatin-induced liver sinusoidal obstruction syndrome

Research Project

Project/Area Number 16H07357
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionKindai University

Principal Investigator

TATSUMI Kohei  近畿大学, 医学部, 講師 (70555432)

Research Collaborator KAJI Hiroshi  近畿大学, 医学部, 教授 (90346255)
Mackman Nigel  University of North Carolina at Chapel Hill, Professor
Project Period (FY) 2016-08-26 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords肝類洞閉塞症候群 / 凝固因子 / 線溶因子 / PAI-1 / 組織因子 / TF / オキサリプラチン / 組織因子 (TF) / ADAMTS13 / 凝固 / 線溶 / tissue factor
Outline of Final Research Achievements

The objective of this study was to clarify the role of coagulation and fibrinolysis system, especially plasminogen activator inihibitor-1 (PAI-1) and tissue factor (TF), in the diathesis of oxaliplatin-induced liver sinusoidal obstruction syndrome (SOS).
Repeated administration of oxaliplatin to the wild-type mice significantly increased PAI-1 mRNA levels in the liver, whereas TF mRNA levels were decreased. The increase rate of liver PAI-1 mRNA was significantly and negatively correlated with the rate of body weight loss of the mice.The increases of inflammatory cytokines and fibrosis markers in the liver of PAI-1 deficient mice were milder than WT mice. TF-deficient mice showed higher mortality and severe body weight loss compared with WT mice.
Therefore, in the SOS pathogenesis, PAI-1 may play an important role in accelerating liver injury by forming multiple microthrombi in the liver microcirculation, resulting in enhanced inflammation and fibrosis.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • Research Products

    (17 results)

All 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] ノースカロライナ大学チャペルヒル校(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Adult hepatocytes direct liver organogenesis through non-parenchymal cell recruitment in the kidney.2018

    • Author(s)
      Utoh R, Komori J, Kuge H, Tatsumi K, Yamada M, Hirohashi S, Tsutsumi M, Amanuma T, Yoshioka A, Nakajima Y, Wake K, Okano T, Lagasse E, Ohashi K.
    • Journal Title

      J Hepatol.

      Volume: 68 Issue: 4 Pages: 744-753

    • DOI

      10.1016/j.jhep.2017.12.016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of Macrophages and Plasminogen Activator Inhibitor-1 in Delayed Bone Repair in Diabetic Female Mice2018

    • Author(s)
      Shimoide Takeshi、Kawao Naoyuki、Tamura Yukinori、Okada Kiyotaka、Horiuchi Yoshitaka、Okumoto Katsumi、Kurashimo Shinji、Ishida Masayoshi、Tatsumi Kohei、Matsuo Osamu、Kaji Hiroshi
    • Journal Title

      Endocrinology

      Volume: 159 Issue: 4 Pages: 1875-1885

    • DOI

      10.1210/en.2018-00085

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of irisin in the linkage from muscle to bone during mechanical unloading in mice2018

    • Author(s)
      Kawao N, Moritake A, Tatsumi K, Kaji H
    • Journal Title

      Calcified Tissue International

      Volume: - Issue: 1 Pages: 24-34

    • DOI

      10.1007/s00223-018-0387-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of follistatin in muscle and bone alterations induced by gravity change in mice.2018

    • Author(s)
      Kawao N, Morita H, Obata K, Tatsumi K, Kaji H.
    • Journal Title

      J Cell Physiol.

      Volume: 233 Issue: 2 Pages: 1191-1201

    • DOI

      10.1002/jcp.25986

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protease-Activated Receptor 1 Enhances Poly I:C Induction of the Antiviral Response in Macrophages and Mice.2017

    • Author(s)
      Antoniak S, Tatsumi K, Bode M, Vanja S, Williams JC, Mackman N
    • Journal Title

      J Innate Immun.

      Volume: 9 Issue: 2 Pages: 181-192

    • DOI

      10.1159/000450853

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation.2017

    • Author(s)
      Tatsumi K, Okano T
    • Journal Title

      Curr Transplant Rep.

      Volume: 4 Issue: 3 Pages: 184-192

    • DOI

      10.1007/s40472-017-0156-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasminogen activator inhibitor-1 deficiency enhances subchondral osteopenia after induction of osteoarthritis in mice.2017

    • Author(s)
      Moritake A, Kawao N, Okada K, Tatsumi K, Ishida M, Okumoto K, Matsuo O, Akagi M, Kaji H.
    • Journal Title

      BMC Musculoskelet Disord.

      Volume: 18 Issue: 1 Pages: 392-392

    • DOI

      10.1186/s12891-017-1752-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of hypergravity on gene levels in anti-gravity muscle and bone through the vestibular system in mice.2017

    • Author(s)
      Kawao N, Morita H, Nishida K, Obata K, Tatsumi K, Kaji H.
    • Journal Title

      J Physiol Sci.

      Volume: - Issue: 5 Pages: 609-616

    • DOI

      10.1007/s12576-017-0566-4

    • NAID

      40021645358

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞シート工学を用いた血友病新規治療2017

    • Author(s)
      辰巳公平、大橋一夫
    • Journal Title

      Frontiers in Haemophilia

      Volume: 4 Pages: 19-24

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 肝細胞移植による血友病治療2017

    • Author(s)
      辰巳公平、大橋一夫
    • Journal Title

      Frontiers in Haemophilia

      Volume: 4 Pages: 17-22

    • Related Report
      2017 Annual Research Report
  • [Presentation] 重症H1N1インフルエンザAウィルス感染患者の予後予測マーカーとしての血漿中マイクロパーティクル由来組織因子活性値とインターロイキン-8値の有用性2017

    • Author(s)
      辰巳公平
    • Organizer
      第17回TTMフォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 凝固因子発現からみた血管内皮積層化培養肝細胞の機能評価2017

    • Author(s)
      辰巳公平
    • Organizer
      第16回日本再生医療学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The role of hepatocyte tissue factor in the hypercoagulable state observed in chronic liver injury2017

    • Author(s)
      辰巳公平
    • Organizer
      第94回日本生理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Role of coagulation factors in a mouse model of influenza virus infection2017

    • Author(s)
      辰巳公平
    • Organizer
      第39回日本血栓止血学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Anticoagulants increase alveolar hemorrhage after influenza A infection in mice2017

    • Author(s)
      Kohei Tatsumi
    • Organizer
      第26回国際血栓止血学会(Inernational Society on Thrombosis and Haemostasis;ISTH)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hepatocyte tissue factor contributes to the hypercoagulable state in chronic liver injury of mice2017

    • Author(s)
      辰巳公平
    • Organizer
      第79回日本血液学会
    • Related Report
      2017 Annual Research Report

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Published: 2016-09-02   Modified: 2020-01-20  

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