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The role of intermediateted filament proteins in hepatic stellate cells in the development of liver fibrosis and hepatocellular carcinoma

Research Project

Project/Area Number 18591513
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionHyogo College of Medicine

Principal Investigator

UYAMA Naoki  Hyogo College of Medicine, Faculty of Medicine, Professor (70402873)

Co-Investigator(Kenkyū-buntansha) FUJIMOTO Jiro  Hyogo College of Medicine, Faculty of Medicine, Professor (90199373)
IIMURO Yuji  Hyogo College of Medicine, Faculty of Medicine, Associate Professor (30252018)
KAWADA Norifumi  Osaka City University, Graduate school of Medine, Faculty of Medicine, Professor (30271191)
IKEDA Kazuo  Osaka City University, Graduate school of Medine, Faculty of Medicine, Associate Professor (80275247)
HATANO Etsuro  Kyoto University, Graduate school of Medine, Faculty of Medicine, Instructor (80359801)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsIntermediate filament / liver fibrois / hepatic stellate cells / hepatocellular carcinoma / synemin / vimentin
Research Abstract

(A) Expression of Intermediate filament proteins by rat hepatic stellate cells.
Expression of intermediated filament proteins in rat normal or cirrhotic liver tissues was investigated. In normal liver, GFAP, desmin, vimentin and synemin were expressed by hepatic stellate cells. In cirrhotic liver, expression of GFAP and synemin was down-regulated and expression of desmin and vimentin was up-regulated. Isolated stellate cells from rat liver are thought to be activated during the culture on the plastic dish. Expression of GFAP and synemin was down-regulated and expression of desmin and vimentin was up-regulated during the culture. So, we found that quiescent rat stellate cells express synmin and GFAP and activated stellate cells express desmin and vimentin.
(B) Expression of Intermediate filament proteins by human hepatic stellate cells.
Expression of GFAP, synemin, desmin and vimentin in human normal or cirrhotic liver tissues was investigated. In normal liver, vimentin and synemin were expressed by hepatic stellate cells. However, desmin and GFAP were not expressed by hepatic stellate cells. In cirrhotic liver, expression of synemin was down-regulated and expression of vimentin was up-regulated. In LX-2 cells, cell line of stellate cells, Expression of vimentin, but not synemin, detected. So, we found that synmin and vimentin play a key role to regulate the activation of hepatic stellate cells.
(C) The role of vimentin in human hepatic stellate cells.
We investigated the role of vimentin in human hepatic stellate cells. Expression of vimentin in LX-2 cells were down regulated by 85% of control by siRNAs. Depletion of vimentin did not affect the ability to proliferate and the expression of type I collagen. In the future, we will investigate the function of vimentin in human hepatic stellate cells again by other methods.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (24 results)

All 2008 2007 2006

All Journal Article (15 results) (of which Peer Reviewed: 6 results) Presentation (9 results)

  • [Journal Article] 切除不能肝細胞癌に対する微粉末シスプラチンを用いた肝動脈塞栓化学療法の効果及び有害事象の検討2008

    • Author(s)
      宇山 直樹, 波多野 悦朗, など
    • Journal Title

      癌と化学療法 35

      Pages: 775-780

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Efficacy and toxicity of transcatheter arterial chemoembolization with Cisplatin suspended in lipiodol for unresectable hepatocellular carcinoma2008

    • Author(s)
      Uyama N, Hatano E, Maetani Y, Isoda H, Shibata T, Taura K, Oe S, Naito M, Yasuchika K, Fujii H, Ikai I, Uemoto S.
    • Journal Title

      Gan To Kagaku Ryoho 35(5)

      Pages: 775-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 切除不能肝細胞癌に対する微粉末シスプラチンを用いた肝動脈塞栓化学療法の効果及び有害事象の検討2008

    • Author(s)
      宇山 直樹、波多野 悦朗, など
    • Journal Title

      癌と化学療法 (In press)

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Expression of somatostatin receptors in splanchnic blood vessels of normal and cirrhotic rats2007

    • Author(s)
      Reynaert H, van Rosse E, Uyama N, et. al.
    • Journal Title

      Liver International 27(6)

      Pages: 825-831

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats.2007

    • Author(s)
      Kinoshita K, Iimuro Y, Otogawa K, Saika S, Inagaki Y, Nakajima Y, Kawada N, Fujimoto J, Friedman SL, Ikeda K.
    • Journal Title

      Gut 56(5)

      Pages: 706-14

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Targeted and regulable expression of transgenes in hepatic stellate cells and myofibroblasts in culture and in vivo using an adenoviral Cre/loxP system to antagonise hepatic fibrosis.2007

    • Author(s)
      Kinoshita K, Iimuro Y, Fujimoto J, Inagaki Y, Namikawa K, Kiyama H, Nakajima Y, Otogawa K, Kawada N, Friedman SL, Ikeda K.
    • Journal Title

      Gut 56(3)

      Pages: 396-404

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of somatostatin receptors in splanchnic blood vessels of norural and cirrhotic rats2007

    • Author(s)
      Reynaert H, van Rosse E, Uyama N, et. al.
    • Journal Title

      Liver International 27(6)

      Pages: 825-831

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection:an analysis of 610 patients over 16 years old2006

    • Author(s)
      Taura K, Hatano E, Uyama N, et. al.
    • Journal Title

      Annals of surgery 244(2)

      Pages: 265-273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prognostic index for patients with hepatocellular carcinoma combined with tumor thrombosis in the major portal vein2006

    • Author(s)
      Ikai I, Hatano E, Uyama N, et. al.
    • Journal Title

      Journal of the American College of Surgeons 202(3)

      Pages: 431-438

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hepatic stellate cells express synemin,a protein bridging intermediate filaments to focal adhesions2006

    • Author(s)
      Uyama N, et. al.
    • Journal Title

      Gut 55(9)

      Pages: 1276-1289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prognostic index for patients with hepatocellular carcinoma combined with tumor thrombosis in the major portal vein.2006

    • Author(s)
      Ikai I, Hatano E, Hasegawa S, Fujii H, Taura K, Uyama N, Shimahara Y.
    • Journal Title

      J Am Coll Surg 202(3)

      Pages: 431-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions.2006

    • Author(s)
      Uyama N, Zhao L, Van Rossen E, Hirako Y, Reynaert H, Adams DH, Xue Z, Li Z, Robson R, Pekny M, Geerts A.
    • Journal Title

      Gut 55(9)

      Pages: 1276-89

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Implication of trequent local ablation therapy for intrahepatic recurrence in prolonged survival ofpatients with hepatocellular carcinoma undergoing hepatic resection : an analysis of 610 patients over 16 years old.2006

    • Author(s)
      Taura K, Hatano E, Uyama N et al.
    • Journal Title

      Annals of surgery 244・2

      Pages: 265-273

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prognostic index for patients with hepatocellular carcinoma combined with tumor thrombosis in the major portal vein.2006

    • Author(s)
      Ikai I, Hatano E, Uyama N et al.
    • Journal Title

      Journal of the American College of Surgeons 202・3

      Pages: 431-438

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions.2006

    • Author(s)
      Uyama N et al.
    • Journal Title

      Gut 55・9

      Pages: 1276-1289

    • Related Report
      2006 Annual Research Report
  • [Presentation] Expression and function of synemin in rat and human hepatic stellate cells2007

    • Author(s)
      Uyama, N
    • Organizer
      42nd Congress of the European Society for Surgical Research
    • Place of Presentation
      Rotterdam,The Nether lands.
    • Year and Date
      2007-05-23
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The Expression And The Fuction Of Synemin In Rat And Human Hepatic Stellate Cells2007

    • Author(s)
      宇山 直樹
    • Organizer
      42nd Congress of the European Society for surgical research(ESSR)
    • Place of Presentation
      The Netherlands
    • Year and Date
      2007-05-23
    • Related Report
      2007 Annual Research Report
  • [Presentation] 切除不能肝細胞癌に対するアイエーコールを用いた肝動脈化学塞栓療法の治療効果及び有害事象の検討2007

    • Author(s)
      宇山 直樹
    • Organizer
      第107回日本外科学会定期学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression and function of synemin in rat and human hepatic stellate cells.2007

    • Author(s)
      Uyama, N., limuro, Y., Fujimoto, J., Geerts, A.
    • Organizer
      First Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association
    • Place of Presentation
      Fukuoka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression and function of synemin in rat and human hepatic stellate cells.2007

    • Author(s)
      Uyama, N., Reynaert, H., Iimuro, Y., Fujimoto, J., Geerts, A.
    • Organizer
      42nd Congress of the European Society for Surgical Research(ESSR)
    • Place of Presentation
      Rotterdam, The Netherlands
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression and function of synemin in rat and human hepatic stellate cells2006

    • Author(s)
      Uyama, N
    • Organizer
      13th International Symposium on Cells of the Hepatic Sinusoid
    • Place of Presentation
      Nigata Japan
    • Year and Date
      2006-09-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 肝細胞癌に対して粉末CDDPを用いた肝動脈塞栓療法を行い,肺転移巣にも著効を認めた2例2006

    • Author(s)
      宇山 直樹
    • Organizer
      第61回日本消化器外科学会定期学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-07-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Hepatocyte growth factor promotes remodeling of murine liver fibrosis accelerating recruitment of bone marrow -derived cells into the liver.2006

    • Author(s)
      limuro, Y. Asano, Y., Son, G., Hirano, T., Fujimoto, J.
    • Organizer
      The American Association for the Study of Liver Diseases'(AASLD) Basic Research Single Topic Conference Hepatic Fibrosis
    • Place of Presentation
      Warrenton, U.S.A.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] NF-KB decoy ameliorates CC14-induced liver injury and fibrosis.2006

    • Author(s)
      Son, G., limuro, Y., Hirano, T., Fujimoto, J.
    • Organizer
      The American Association for the Study of Liver Diseases'(AASLD) Basic Research Single Topic Conference Hepatic Fibrosis
    • Place of Presentation
      Warrenton, U.S.A
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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