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Impact of autophagy in liver regeneration

Research Project

Project/Area Number 23591989
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

YOSHIZUMI Tomoharu  九州大学, 大学病院, 講師 (80363373)

Co-Investigator(Kenkyū-buntansha) SHIRABE Ken  九州大学, 医学研究院, 准教授 (70264025)
IKEGAMI Toru  九州大学, 医学研究院, 助教 (80432938)
YAMASHITA Yo-ichi  九州大学, 医学研究院, 助教 (00404070)
HARIMOTO Norifumi  九州大学, 医学研究院, 助教 (00419582)
UCHIYAMA Hideaki  九州大学, 医学研究院, その他 (70380425)
SOEJIMA Yuji  九州大学, 医学研究院, 共同研究員 (30325526)
NINOMIYA Mizuki  九州大学, 医学研究院, 助教 (30546461)
TAKETOMI Akinobu  九州大学, 医学研究院, 講師 (70363364)
MAEHARA Yoshihiko  九州大学, 医学研究院, 教授 (80165662)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肝臓外科学 / オートファジー / 肝再生
Research Abstract

We investigated the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx) in liver-specific autophagy-related gene 5 (Atg5) knockout (KO) mice. Liver regeneration was severely impaired by 70% PHx, with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx induced intracellular adenosine triphosphate and beta-oxidation reduction as well as injured cellular mitochondria. Furthermore, PHx in Atg5 KO mice enhanced hepatic accumulation of p62 and ubiquitinated proteins. These results indicated that reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver of these mice. Up-regulation of p21 was associated with hepatocyte senescence, senescence-associated b-galactosidase expression, irreversible growth arrest, and secretion of senescence-associated molecules, including interleukin (IL)-6 and IL-8.

Report

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

    (36 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 2 results) Presentation (22 results)

  • [Journal Article] Re-evaluation of the predictive score for 6-month graft survival in living donor liver transplantation in the modern era.2014

    • Author(s)
      Yoshizumi T, Ikegami T, Bekki Y, Ninomiya M, Uchiyama H, Iguchi T, Yamashita Y, Kawanaka H, Shirabe K, Maehara Y.
    • Journal Title

      Liver Transpl.

      Volume: 20 Issue: 3 Pages: 323-32

    • DOI

      10.1002/lt.23804

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Skeletal muscle area correlates with body surface area in healthy adults.2014

    • Author(s)
      Yoshizumi T, Shirabe K, Nakagawara H, Ikegami T, Harimoto N, Toshima T, Yamashita Y, Ikeda T, Soejima Y, Maehara Y.
    • Journal Title

      Hepatol Res.

      Volume: 44 Issue: 3 Pages: 313-8

    • DOI

      10.1111/hepr.12119

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis.2014

    • Author(s)
      Yoshizumi T, Shirabe K, Ikegami T, Yamashita N, Mano Y, Yoshiya S, Matono R, Harimoto N, Uchiyama H, Toshima T, Maehara Y.
    • Journal Title

      Transpl Infect Dis.

      Volume: 16 Issue: 2 Pages: 225-31

    • DOI

      10.1111/tid.12188

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy enhances hepatocellular carcinoma progression by activation of mitochondrialβ-oxidation2014

    • Author(s)
      Toshima T, Shirabe K, Matsumoto Y, Yoshiya S, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y.
    • Journal Title

      J Gastroenterol

      Volume: 49(5) Issue: 5 Pages: 907-16

    • DOI

      10.1007/s00535-013-0835-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of autophagy during liver regeneration impairs energy charge and hepatocyte senescence in mice.2014

    • Author(s)
      Toshima T1, Shirabe K, Fukuhara T, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Okano S, Maehara Y.
    • Journal Title

      Hepatology.

      Volume: 印刷中 Issue: 1 Pages: 25-25

    • DOI

      10.1002/hep.27140

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy enhances hepatocellular carcinoma progression by activation of mitochondrial β-oxidation.2014

    • Author(s)
      Toshima T1, Shirabe K, Matsumoto Y, Yoshiya S, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y.
    • Journal Title

      J Gastroenterol.

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma.2013

    • Author(s)
      Yoshizumi T, Ikegami T, Toshima T, Harimoto N, Uchiyama H, Soejima Y, Yamashita Y, Shirabe K, Maehara Y.
    • Journal Title

      Transplant Proc.

      Volume: 45 Issue: 9 Pages: 3310-3

    • DOI

      10.1016/j.transproceed.2013.05.001

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma.2013

    • Author(s)
      Yoshizumi T, Ikegami T, Yoshiya S, Motomura T, Mano Y, Muto J, Ikeda T, Soejima Y, Shirabe K, Maehara Y.
    • Journal Title

      Hepatol Res.

      Volume: 43 Issue: 7 Pages: 709-16

    • DOI

      10.1111/hepr.12016

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment.2013

    • Author(s)
      Motomura T, Yoshizumi T, et al
    • Journal Title

      Journal of Hepatology

      Volume: 58 Issue: 1 Pages: 58-64

    • DOI

      10.1016/j.jhep.2012.08.017

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of human T-cell leukemia virus type 1 in living donor liver transplantation2012

    • Author(s)
      Yoshizumi T, et al
    • Journal Title

      American Journal of Transplantation

      Volume: 12 Issue: 6 Pages: 1479-85

    • DOI

      10.1111/j.1600-6143.2012.04037.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk factors that increase Mortality after living donor liver transplantation.2012

    • Author(s)
      Yoshizumi T, et al
    • Journal Title

      Transplantation

      Volume: 93 Issue: 1 Pages: 93-8

    • DOI

      10.1097/tp.0b013e318238dacd

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation.2012

    • Author(s)
      Ikegami T, Yoshizumi T, et al
    • Journal Title

      Liver Transplantation

      Volume: 18 Issue: 9 Pages: 1060-8

    • DOI

      10.1002/lt.23483

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk factors that increase mortality after living donor liver transplantation.2012

    • Author(s)
      Yoshizumi T, et al.
    • Journal Title

      Transplantation

      Volume: 93 Pages: 93-8

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Living donor liver transplantation in patients who have received pretransplant treatment for hepatocellular carcinoma.2012

    • Author(s)
      Yoshizumi T, et al.
    • Journal Title

      Transplantation

      Volume: 91

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 肝癌に対する生体肝移植の新たな適応基準に関する検討2013

    • Author(s)
      吉住朋晴
    • Organizer
      49回日本移植学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 肝移植後の短期予後改善を目指した我々の治療戦略2013

    • Author(s)
      吉住朋晴
    • Organizer
      第68回日本消化器外科学会総会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Annual Research Report
  • [Presentation] 生体肝移植レシピエント手術による高度技能医育成に関する検討2013

    • Author(s)
      吉住朋晴
    • Organizer
      第25回日本肝胆膵外科学会総会
    • Place of Presentation
      宇都宮
    • Related Report
      2013 Annual Research Report
  • [Presentation] 肝移植後の短期予後改善を目指した我々の治療戦略2013

    • Author(s)
      吉住朋晴
    • Organizer
      第49回日本肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 肝移植の成績向上に向けた我々のチーム作りへの取り組み2013

    • Author(s)
      吉住朋晴
    • Organizer
      第38回日本外科系連合学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 生体肝移植後長期成績向上のための治療戦略の構築:原疾患治療を目指して2012

    • Author(s)
      吉住朋晴
    • Organizer
      日本消化器外科学会
    • Place of Presentation
      富山
    • Related Report
      2012 Research-status Report
  • [Presentation] 当科における脳死肝移植待機患者の現状と脳死肝移植の適応に関する検討2012

    • Author(s)
      吉住朋晴
    • Organizer
      日本肝臓学会
    • Place of Presentation
      金沢
    • Related Report
      2012 Research-status Report
  • [Presentation] Expanded selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma2012

    • Author(s)
      Tomoharu Yoshizumi
    • Organizer
      Annual conference: International Liver Cancer Association
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨格筋面積の標準値算出式に関する検討2012

    • Author(s)
      吉住朋晴
    • Organizer
      日本コンピューター外科学会
    • Place of Presentation
      徳島
    • Related Report
      2012 Research-status Report
  • [Presentation] 好中球/リンパ球比を用いた、肝癌に対する生体肝移植後の再発予測に関する検討2012

    • Author(s)
      吉住朋晴
    • Organizer
      日本消化器癌発生学会
    • Place of Presentation
      徳島
    • Related Report
      2012 Research-status Report
  • [Presentation] 急性肝不全に対する総合的治療戦略2011

    • Author(s)
      吉住朋晴
    • Organizer
      日本消化器病学会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 脳死肝移植の適応に関する検討2011

    • Author(s)
      吉住朋晴
    • Organizer
      日本肝臓学会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 右葉グラフトを用いた生体肝移植2011

    • Author(s)
      吉住朋晴
    • Organizer
      日本消化器外科学会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] 肝再生におけるオートファジーの意義2011

    • Author(s)
      戸島剛男、吉住朋晴
    • Organizer
      日本肝臓学会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] Living donor liver transplantation: lessons learned form 318 consecutive cases2011

    • Author(s)
      Yoshizumi T
    • Organizer
      Annual congress of International liver transplantation society
    • Place of Presentation
      スペイン
    • Related Report
      2011 Research-status Report
  • [Presentation] 肝細胞癌に対する新たな肝移植適応基準の検討2011

    • Author(s)
      吉住朋晴
    • Organizer
      日本癌治療学会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] 肝移植の治療成績向上を目指した我々の新しい取り組みと展望2011

    • Author(s)
      吉住朋晴
    • Organizer
      日本消化器関連学会週間
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Presentation] 肝再生におけるオートファジーの生物学的意義

    • Author(s)
      戸島剛男, 調憲, 吉屋匠平, 武藤純, 的野る美, 間野洋平, 池上徹, 吉住朋晴, 前原喜彦
    • Organizer
      日本消化器外科学会総会67回
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝再生の機序解明と臨床への応用肝再生におけるオートファジーの生物学的意義

    • Author(s)
      戸島剛男, 調憲, 吉屋匠平, 播本憲史, 山下洋市, 池上徹, 内山秀昭, 吉住朋晴, 副島雄二, 前原喜彦
    • Organizer
      日本外科学会総会114回
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝分化/再生/幹細胞肝再生におけるオートファジーの生物学的意義

    • Author(s)
      戸島剛男, 調憲, 吉屋匠平, 武藤純, 的野る美, 間野洋平, 森田和豊, 萱島寛人, 池上徹, 吉住朋晴, 前原喜彦
    • Organizer
      肝臓学会総会49回
    • Related Report
      2013 Final Research Report
  • [Presentation] 侵襲に対する生体反応とその制御肝再生におけるオートファジーの意義

    • Author(s)
      戸島剛男, 調憲, 武冨紹信, 間野洋平, 武藤純, 的野る美, 吉屋匠平, 森田和豊, 萱島寛人, 池上徹, 吉住朋晴, 前原喜彦
    • Organizer
      日本外科学会総会113回
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝細胞癌進展におけるオートファジーの意義

    • Author(s)
      戸島剛男, 調憲, 武冨紹信, 本村貴志, 間野洋平, 武藤純, 的野る美, 吉屋匠平, 森田和豊, 萱島寛人, 池上徹, 吉住朋晴, 前原喜彦
    • Organizer
      日本癌治療学会総会51回
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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