| Project/Area Number |
17390375
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
FUJIMOTO Jiro Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (90199373)
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| Co-Investigator(Kenkyū-buntansha) |
IIMURO Yuji Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30252018)
YAMANAKA Juniti Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90289083)
HIRANO Tadamiti Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (90340968)
OKADA Toshihiro Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (70351799)
NAKANISHI Kenji Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (60172350)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2006: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | angiogenesis / HGF / NK4 / VEGF / sFlt-1 / liver regeneration / NK4 |
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| Research Abstract |
We investigated the influence of anti-angiogenesis for hepatic regeneration using HGF antagonist (NK4) and suppressor of VEGF receptor (sFlt-1). NK4 expressing adenoviral vector (Ad.NK4) or sFlt-1 expressing adenoviral vector (Ad.sFlt-1) were infected mice liver. Seventy percent hepatectomy was performed 48 hours after infection. LacZ expressing adenoviral vector (Ad.LacZ) was used as control. Expression of Nk4 or sFlt-1 reached maximum level 48 hours after infection (NK4: 300ng/ml, sFlt-1:350ng/ml) and sustained for 2 weeks. Remnant liver was removed at 12, 24, 36, 48, 72 and 120 hrs after partial hepatectomy, and hepatic regeneration was assessed. As a result, increase of remnant hepatic weight was significantly delayed in Ad.NK4 or Ad.sFlt-1 infected mice. Results of mitotic cells and BrdU index showed significant delay of hepatic regeneration in Ad.NK4 or Ad.sFlt-1 infected mice at 48 or 36 hours after hepatectomy. Immnuhistochemical staining of CD31 showed suppression of sinusoidal endothelial cells growth in Ad.NK4 infected mice. Ang-1, Ang-2, Tie-1, and Tie-2 are considered to be crucial in the process of maturation of vessels. Real time PCR showed suppression of mRNA of Ang-1, Ang-2, Tie-1, and Tie-2 with significant difference. These results suggested that hepatic regeneration after hepatectomy closely correlates with angiogenesis.
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