| Project/Area Number |
13670517
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
TAMURA Shinji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30243223)
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| 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
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| 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)
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| Keywords | liver 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 |
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| 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.
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