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2008 Fiscal Year Final Research Report

Pathogenesis of progressive bile duct loss in primary biliary cirrhosis : A possible involvement of cellular senescence

Research Project

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Project/Area Number 18590325
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKanazawa University

Principal Investigator

SASAKI Motoko  Kanazawa University, 医学系, 准教授 (70225895)

Co-Investigator(Renkei-kenkyūsha) SATO Yasunori  金沢大学, 医学系, 講師 (30324073)
NAKANUMA Yasuni  金沢大学, 医学系, 教授 (10115256)
Project Period (FY) 2006 – 2008
Keywords病理学 / 再生医学 / 細胞老化 / 原発性胆汁性肝硬変 / 胆管上皮細胞 / 免疫組織化学
Research Abstract

本研究では, 原発性胆汁性肝硬変(PBC)における胆管消失に胆管細胞老化が関与することが明らかとなった. 人体材料を用いた検討では, PBCの傷害肝内小型胆管では高率に細胞老化マ-カ- : SA-ss-gal, p16^(INK4a), p21^(WAF1/Cip)の発現, テロメア長短縮を認めた. さらに酸化ストレス, 炎症性サイトカインにより培養胆管細胞に細胞老化が誘導され, その分子機構にはp16^<INK4a> 発現抑制因子bmi1発現低下、ATM /p53/p21経路経路が関与することが明らかとなった.

Research Products

(18 results)

All 2008 2007 2006

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (8 results)

  • [Journal Article] Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence2008

    • Author(s)
      Sasaki M, Ikeda H, Yamaguchi J, et.al.
    • Journal Title

      Hepatology 48

      Pages: 186-195

    • Peer Reviewed
  • [Journal Article] Proinflammatory cytokine-induced cellular senescence of biliary epithelial cells is mediated via oxidative stress and activation of ATM pathway : a culture study2008

    • Author(s)
      Sasaki M, Ikeda H, Sato Y, et.al.
    • Journal Title

      Free Radic Res 42

      Pages: 625-632

    • Peer Reviewed
  • [Journal Article] Activation of ATM signaling pathway is involved in oxidative stress-induced expression of mitoinhibitory p^<21WAF1/Cip1> in chronic non-suppurative destructive cholangitis in primary biliary cirrhosis : an immunohistochemical study2008

    • Author(s)
      Sasaki M, Ikeda H, Nakanuma Y
    • Journal Title

      J Autoimmun 31

      Pages: 73-78

    • Peer Reviewed
  • [Journal Article] Over-expression of polycomb group protein EZH2 relates to decreased expression of p16 INK4a in cholangiocarcinogenesis in hepatolithiasis2008

    • Author(s)
      Sasaki M, Yamaguchi J, Itatsu K, et.al.
    • Journal Title

      J Pathol 215

      Pages: 175-183

    • Peer Reviewed
  • [Journal Article] The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression andaggressive biological behavior of hepatocellular carcinoma2008

    • Author(s)
      Sasaki M, Ikeda H, Itatsu K, et.al.
    • Journal Title

      Lab Invest 88

      Pages: 873-882

    • Peer Reviewed
  • [Journal Article] Tumor necrosis factor-alpha induces the aberrant expression of mucus core protein-2 in non-neoplastic biliary epithelial cells via the upregulation of CDX2 in chronic cholangitis2008

    • Author(s)
      Ikeda H, Sasaki M, Ohira S, et.al.
    • Journal Title

      Hepatol Res 38

      Pages: 1006-17

    • Peer Reviewed
  • [Journal Article] Naturally-occurring regulatory T cells are increased in inflamed portal tracts with cholangiopathy in primary biliary cirrhosis2007

    • Author(s)
      Sasaki M, Ikeda H, Sawada S, et.al.
    • Journal Title

      J Clin Pathol 60

      Pages: 1102-1107

    • Peer Reviewed
  • [Journal Article] Interaction of Toll-like receptors with bacterial components induces expression of CDX2 and MUC2 in rat biliary epithelium in vivo and in culture2007

    • Author(s)
      Ikeda H, Sasaki M, Ishikawa A, et.al.
    • Journal Title

      Lab Invest 87

      Pages: 559-571

    • Peer Reviewed
  • [Journal Article] Decreased expression of Bmi1 is closely associated with cellular senescence in small bile ducts in primary biliary cirrhosis2006

    • Author(s)
      Sasaki M, Ikeda H, Sato Y, et.al.
    • Journal Title

      Am J Pathol 169

      Pages: 831-845

    • Peer Reviewed
  • [Journal Article] Augmented expression of hepatocytes growth factor activator inhibitor type 1 (HAI-1) in intrahepatic small bile ducts in primary biliary cirrhosis2006

    • Author(s)
      Sasaki M, Ikeda H, Kataoka H, et.al.
    • Journal Title

      Virchows Arch 449

      Pages: 462-471

    • Peer Reviewed
  • [Presentation] Cellular senescence of bile ductular cells may be involved in the pathophysiology in ductular reactions in chronicliver diseases. 59th Annual Meeting of the American Association for the Study of Liver Diseases2008

    • Author(s)
      Sasaki M, et.al.
    • Organizer
      AASLD
    • Place of Presentation
      San Francisco
    • Year and Date
      2008-11-01
  • [Presentation] Cellular senescence of biliary epithelial cells characterizes the damaged small bile ducts in primary biliary cirrhosis. 59th Annual Meeting of the American Association for the Study of Liver Diseases2008

    • Author(s)
      Sasaki M, et.al.
    • Organizer
      AASLD
    • Place of Presentation
      San Francisco
    • Year and Date
      2008-11-01
  • [Presentation] 自己免疫性肝疾患研究に創流を求めて自己免疫性肝疾患の胆管病変 (PBC, PSC, AIP の胆管病変)2008

    • Author(s)
      佐々木素子ら
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-04
  • [Presentation] 原発性胆汁性肝硬変の傷害胆管におけるテロメア長短縮とその意義2008

    • Author(s)
      佐々木素子ら
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-03
  • [Presentation] 慢性胆管炎のgoblet cell metaplasiaにおけるMUC2(腸型ムチン)発現の分子機構 tumor necrosisfactor(TNF)-αはCDX2発現を介してMUC2を誘導する2008

    • Author(s)
      池田博子, 佐々木素子ら
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-03
  • [Presentation] 肝障害と修復に関する研究の展開肝線維化におけるendothelial to mesenchymal transition(EndMT)の関与2008

    • Author(s)
      佐藤保則ら
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      松山
    • Year and Date
      2008-06-03
  • [Presentation] 老化機構解明のための病理学的アプローチ 肝疾患における細胞老化の関与自己免疫性疾患から発癌まで2008

    • Author(s)
      佐々木素子ら
    • Organizer
      第97回日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-14
  • [Presentation] 原発性胆汁性肝硬変の胆管細胞老化におけるATM (ataxiatelangiectasiamutated)/p53/p21経路の関与2007

    • Author(s)
      佐々木素子ら
    • Organizer
      第43回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-05-31

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Published: 2010-06-09   Modified: 2016-04-21  

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