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Study on gene therapy for liver regeneration. -Effect of gene transduction of soluble HB-EGF and soluble TGF-β type II receptor on liver regeneration-

Research Project

Project/Area Number 13670517
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

TAMURA Shinji  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30243223)

Co-Investigator(Kenkyū-buntansha) IGURA Takumi  Osaka University Hospital, Medical Staff, 医学部附属病院, 医員(臨床研究)
FUKUI Koji  Osaka University Hospital, Medical Staff, 医学部附属病院, 医員(臨床研究)
KISO Shinichi  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40335352)
土井 喜宣  大阪大学, 医学部・附属病院, 医員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsliver regeneration / soluble receptor / soluble HB-EGF / TGF-β / gene therapy / 可溶性TGF-βII型受容体 / 可溶型HB-EGF / HVJ-リポソーム
Research Abstract

Acceleration of liver regeneration is important for the treatment of hepatic failure. We have reported that HB-EGF is a potent mitogen of hepatocyte and plays an important role in liver regeneratian. On the other hands, TGF-β, a growth inhibitory factor stimulates apoptosis of hepatocyte and inhibits liver regeneration.
In this study, we demonstrated that NF-kB is activated in hepatic non-parenchymal cells after partial hepatectomy and stimulates the expression of HB-EGF gene. We also indicated that soluble form of HB-EGF is essential for liver regeneration using HB-EGF transgenic mice.
To develop the new methods for acceleration the liver regeneration, dual introduction of soluble HB-EGF gene and soluble TGF-βtype II receptor that blocks the action of TGF-β is investigated. We developed the expression plasmid containing soluble TGF-βtype II receptor cDNA attached with human immunoglobulin Fc region or soluble HB-EGF cDNA. Both genes were introduced into mice skeletal muscle using in vivo electroporation methods. The plasma concentration of soluble HB-EGF and soluble TGF-β type II receptor were measured with newly developed ELISA systems. Pretreatment with hyaluronidase increased the expression levels and obtains 6-fold higher concentrations of soluble HB-EGF or soluble TGF-βtype II receptor.
Our results give a basis for development of the gene therapy to accelerate the liver regeneration.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] S.Sakuda, S.Tamura, et al.: "NF-kappaB activation in non-parenchymal liver cells after partial hepatectomy in rats : possible involvement in expression of heparin-binding epidermal growth factor-like growth factor"J. Hepatol.. 36. 527-533 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Sakuda, S.Tamura, et al.: "Activation of signal transducer and activator of transcription 3 and expression of suppressor of cytokine signal 1 during liver regeneration in rats"J. Hepatol.. 36. 378-384 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Kiso, et al.: "Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy"Gastroenterology. 124. 701-707 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S. Sakuda, S. Tamura, A. Yamada, J. Miyagawa, K. Yamamoto, S. Kiso, N. Ito, S. Higashiyama, N. Taniguchi, S. Kawata, Y. Matsuzawa: "NF-kappaB activation in non-parenchymal liver cells after partial hepatectomy in rats: possible involvement in expression of heparin-binding epidermal growth factor-like growth factor"J Hepatol.. 36(4). 527-533 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S. Sakuda, S. Tamura, A. Yamada, J. Miyagawa, K. Yamamoto, S. Kiso, N. Ito, K. Imanaka, A. Wada, T. Naka, T. Kishimoto, S. Kawata, Y. Matsuzawa: "Activation of signal transducer and activator transcription 3 and expression of suppressor of cytokine signal 1 during liver regeneration in rats"J Hepatol.. 36(3). 378-384 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S. Kiso, S. Kawata, S. Tamura, Y. Inui, Y. Yoshida, Y. Sawai, S. Umeki, N. Ito, A. Yamada, J. Miyagawa, S. Higashiyama, T. Iwawaki, M. Saito, N. Taniguchi, Y. Matsuzawa, K. Kohno: "Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy"Gastroenterology. 124(3). 701-707 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kiso S, Kawata S, et al.: "Transgenic expression of heparin-binding EGF-like growth factor in the mice liver accelerates the proliferation oh hepatocytes after partial hepatectomy"Gastroentreology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakada S, Tamura S, et al.: "NF-kappaB activation an non-parenchymal liver cells after partial hepatectomy in rats : possible involvement in expression of heparin-binding epidermal growth factor-like growth factor"J Hepatol. 36・4. 527-533 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakuta S, Tamura S et al.: "NF-kB activation in non-parenchymal liver cells after partial hepatectomy in rats : possible involvement in expression of heparin-binding epidermal growth factor-like growth factor"J. Hepatology. (in press). (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakuta S, Tamura S et al.: "Activation of signal transducer and activator transcription 3 and expression of suppressor of cytokine signal 1 during liver regeneration in rats"J. Hepatology. (in press). (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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