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Control of liver fibrosis after transplantation by immunomodulation

Research Project

Project/Area Number 23390322
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKyoto University

Principal Investigator

KOJIRO Taura  京都大学, 医学(系)研究科(研究院), 助教 (80378629)

Co-Investigator(Kenkyū-buntansha) UEMOTO Shinji  京都大学, 医学研究科, 教授 (40252449)
HATANO Etsuro  京都大学, 医学研究科, 講師 (80359801)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2011: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Keywords肝線維化 / 肝移植 / 脾臓 / 免疫 / 肝線進化 / 星細胞 / Helper T細胞 / サイトカイン
Research Abstract

To investigate the effects of splenectomy on liver fibrosis, BALB/c mice underwent splenectomy or sham operation and subjected to carbon tetrachloride (CCl4) or thioacetamide (TAA) treatments. Splenectomy significantly suppressed liver fibrosis in the CCl4 and TAA models. The inhibitory effect of splenectomy on liver fibrosis was not observed in SCID mice.
To investigate the mechanisms underlying these effects, we investigated the change of liver Th1/Th2 balance. As a result, splenectomy shifted Th1/Th2 balance toward Th1-dominance. In addition, the number of CD4+ lymphocytes in the spleen was decreased. In contrast, that in the liver was increased. GFP+ splenic lymphocytes were transplanted into the spleen of wild type mice. GFP+CD4+ lymphocytes appeared in the liver after induction of fibrosis and the vast majority of them were Th2 lymphocytes by flow cytometry.
We conclude that splenectomy suppresses progression of liver fibrosis at least partly through restoring the Th1/Th2 balance.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (23 results)

All 2014 2013 2012 2011

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (12 results)

  • [Journal Article] The impact of posthepatectomy liver failure on the recurrence of hepatocellular carcinoma2014

    • Author(s)
      Iguchi K, Hatano E, Yamanaka K, Tanaka S, Taura K, Uemoto S
    • Journal Title

      World J Surg

      Volume: 38(1) Issue: 1 Pages: 150-158

    • DOI

      10.1007/s00268-013-2247-7

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct volume manipulation for visualizing intraoperative liver resection process2014

    • Author(s)
      Nakao M, Oda Y, Taura K, Minato K
    • Journal Title

      Comput Methods Programs Biomed

      Volume: 113(3) Issue: 3 Pages: 725-735

    • DOI

      10.1016/j.cmpb.2013.12.004

    • NAID

      120005399110

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of olprinone on liver microstructure in rat partial liver transplantation2013

    • Author(s)
      Yamanaka K, Hatano E, Iguchi K, Yamamoto G, Sato M, Toriguchi K, Tanabe K, Takemoto K, Nakamura K, Koyama N, Narita M, Nagata H, Taura K, Uemoto S
    • Journal Title

      J Surg Res

      Volume: 183(1) Issue: 1 Pages: 391-396

    • DOI

      10.1016/j.jss.2012.11.033

    • NAID

      120005298136

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of oral intake of hydrogen water on liver fibrogenesis in mice2013

    • Author(s)
      Koyama Y, Taura K, Hatano E, Tanabe K, Yamamoto G, Nakamura K, Yamanaka K, Kitamura K, Narita M, Nagata H, Yanagida A, Iida T, Iwaisako K, Fujinawa H, Uemoto S
    • Journal Title

      Hepatol Res

      Volume: May 20 Issue: 6 Pages: 663-677

    • DOI

      10.1111/hepr.12165

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Soluble thrombomodulin attenuates sinusoidal obstruction syndrome in rat through suppression of high mobility group box 12013

    • Author(s)
      Nakamura K, Hatano E, Miyagawa-Hayashino A, Okuno M, Koyama Y, Narita M, Seo S, Taura K, Uemoto S
    • Journal Title

      Liver Int

      Volume: Nov 29 Issue: 10 Pages: 1473-1487

    • DOI

      10.1111/liv.12420

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Origin of myofibroblasts in liver fibrosis.2012

    • Author(s)
      Brenner DA
    • Journal Title

      Fibrogenesis Tissue Repair.

      Volume: Jun 6;5 Suppl 1 Issue: S1

    • DOI

      10.1186/1755-1536-5-s1-s17

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sorafenib attenuates monocrotaline-induced sinusoidal obstruction syndrome in rats through suppression of JNK and MMP-9.2012

    • Author(s)
      Nakamura Koijro
    • Journal Title

      J Hepatol.

      Volume: Nov;57(5) Issue: 5 Pages: 1037-43

    • DOI

      10.1016/j.jhep.2012.07.004

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist2012

    • Author(s)
      Iwaisako K, Haimerl M, Paik YH, Taura K, Kodama Y, Sirlin C, Yu E, Yu RT, Downes M, Evans RM, Brenner DA, Schnabl B
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 109 Issue: 21 Pages: 1369-76

    • DOI

      10.1073/pnas.1202464109

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-alcoholic steatohepatitis-induced fibrosis : Toll-like receptors, reactive oxygen species and Jun N-terminal kinase2011

    • Author(s)
      Brenner DA, Seki E, Taura K, Kisseleva T, Deminicis S, Iwaisako K, Inokuchi S, Schnabl B, Oesterreicher CH, Paik YH, Miura K, Kodama Y
    • Journal Title

      Hepatology Research

      Volume: 41 Issue: 7 Pages: 683-686

    • DOI

      10.1111/j.1872-034x.2011.00814.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of the Wnt antagonist Dkk2 links the loss of Sept4 and myofibroblastic transformation of hepatic stellate cells2011

    • Author(s)
      Yanagida A, Iwaisako K, Hatano E, Taura K, Sato F, Narita M, Nagata H, Asechi H, Uemoto S, Kinoshita M
    • Journal Title

      BBA-Molecular Basis of Disease

      Volume: 812 Issue: 11 Pages: 1403-1411

    • DOI

      10.1016/j.bbadis.2011.06.015

    • NAID

      120003517932

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis2011

    • Author(s)
      Kitamura K, Taura K, et al
    • Journal Title

      J Hepatol

      Volume: 4 Pages: 846-857

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Migration of splenic lymphocytes promotes fibrotic response in the liver through modification of T helper cytokine balance in mice2014

    • Author(s)
      K. Tanabe, K. Taura, Y. Koyama, G. Yamamoto, T. Nishio, E. Hatano, S. Uemoto
    • Organizer
      Academic Surgical Congress
    • Place of Presentation
      Manchester Grand Hyatt (San Diego, CA)
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Liver Stiffness Measurement Predicts Posthepatectomy Liver Failure2014

    • Author(s)
      K. Taura, Y. Koyama, K. Tanabe, G. Yamamoto, T. Nishio, E. Hatano, S. Uemoto
    • Organizer
      Academic Surgical Congress
    • Place of Presentation
      Manchester Grand Hyatt (San Diego, CA)
    • Related Report
      2013 Final Research Report
  • [Presentation] 脾臓摘出術は肝臓におけるTh1/Th2 サイトカインバランスの変化を介して肝線維化を抑制する2014

    • Author(s)
      田邉和孝, 田浦康二朗, 波多野悦朗, 小山幸法, 山本玄, 西尾太宏, 奥田雄紀浩, 中村公治郎, 鳥口寛, 竹本研史, 上本伸二
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝静脈根部大型肝癌に対する肝切除術式2014

    • Author(s)
      田浦康二朗, 波多野悦朗, 安近健太郎, 瀬尾智, 福光剣, 上本伸二
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Final Research Report
  • [Presentation] 脾臓摘出術は肝臓におけるTh1/Th2サイトカインバランスの変化を介して肝線維化を抑制する2014

    • Author(s)
      田邉和孝
    • Organizer
      日本外科学会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Liver Stiffness Measurement Predicts Posthepatectomy Liver Failure (PHLF)2014

    • Author(s)
      田浦康二朗
    • Organizer
      Academic Surgical Congress
    • Place of Presentation
      Manchester Grand Hyatt (San Diego, CA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 肝静脈根部大型肝癌に対する肝切除術式2014

    • Author(s)
      田浦康二朗
    • Organizer
      日本外科学会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Three-Dimensional Image of Hepatic Hilum by CT Cholangiography with Carbon Dioxide for Preoperative Assessment of Biliary Malignancies2012

    • Author(s)
      田浦康二朗
    • Organizer
      Internationa Forum of Liver Surgery
    • Place of Presentation
      セイコーグランドホテル(秋田県)
    • Year and Date
      2012-03-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] 3D CT cholangiographyを活用した肝門部胆管癌に対する術式選択と手術プラニング2012

    • Author(s)
      田浦 康二朗
    • Organizer
      日本外科学会総会
    • Place of Presentation
      幕張メッセ(千葉市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Plissimo Eraを用いた 肝切除術のVirtual Reality2012

    • Author(s)
      田浦 康二朗
    • Organizer
      日本消化器外科学会
    • Place of Presentation
      富山国際会議場(富山市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Usefulness of Liver Stiffness Measurement for the Prediction of Posthepatectomy Liver Failure2012

    • Author(s)
      Taura Kojiro
    • Organizer
      The 63rd Annual Meeting of the American Association for the Study of Liver Disease
    • Place of Presentation
      Hynes Convention Center (Boston, USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肝胆膵外科における Virtual 3D画像と 臓器立体モデルへの取り組み2012

    • Author(s)
      田浦 康二朗
    • Organizer
      日本内視鏡外科学会総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2012 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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