| Project/Area Number |
09670544
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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 Medical School, Assistant Professor, 医学部, 助手 (30243223)
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| Co-Investigator(Kenkyū-buntansha) |
KISO Shinichi OSAKA University Hospital, Medial Staff, 医学部・附属病院, 医員
FUKUDA Kazuto OSAKA University Hospital, Medial Staff, 医学部・附属病院, 医員
INUI Yoshiaki OSAKA University Medical School, Associate Professor, 医学部, 助手 (00294067)
KAWATA Sumio Osaka University Medical School, Assistant Professor, 医学部, 助教授 (90183285)
松田 幸彦 大阪大学, 医学部, 助手 (90283770)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | HB-EGF / liver regeneration / hepatocyte / growth factor / in vivo / therapy / HB-EGF / 肝産生 / マウス |
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| Research Abstract |
We have reported that heparin-binding EGF-like growth factor(HB-EGF) is a potent mitogen of hepatocytes in vitro.The level of HB -EGF mRNA in regenerating rat liver increases rapidly after a partial hepatectomy.In vitro study showed that HB-EGF induces the expression of HGF and TGF-alpha in non-parenchymal cells and hepatocytes, respectively.These results indicated that HB-EGF may play an important role in liver regeneration.
In this study, we investigated the plasma HB-EGF levels in patients after partial hepatectomy using enzyme-linked immunosorbent assay.In patients who underwent gross hepatectomy, plasma HB-EGF levels increased, reaching maximal levels approximately 5 to 7 days after surgery, which indicated that HB-EGF may be involved in liver regeneration in human.
We also investigated the effect of administration HB-EGF to mice on proliferation of hepatocyte in vivo.Recombinant HB-EGF were administered intravenously to the normal mice for 4 times at 2h-interval.Proliferation of hepatocyte were determined as labeling index of BrdU.Activation of NE-kB and STAT-3 were studied using gel shift assay.The labeling index is 300-fold higher in HB-EGF administered mice than that of controls.In vivo administration of HB-EGF activated NF-kB and STAT-3 in the liver. The induction of HGF were observed in HB-EGF-administered mice liver.
In summary, in vivo administration of HB-EGF stimulated liver regeneration in normal mice liver, which indicated that HB-EGF could be a therapeutic agent for liver regeneration.
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