| Project/Area Number |
16390210
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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 |
Gastroenterology
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| Research Institution | Okayama University |
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Principal Investigator |
SHIRAHA Hidenori (2005-2006) University Hospital of Medical and Dentistry, Department of Gastroenterology and Hepatology, Research Associate, 医学部・歯学部附属病院, 助手 (40379748)
白鳥 康史 (2004) 岡山大学, 大学院・医歯学総合研究科, 教授 (70196624)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAGUCHI Kohsaku Graduate School of Medicine, Dentistry and Pharmaceutical Science Medicine, Department of Medicine and Medical Science, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (90235143)
TAKAKI Akinobu University Hospital of Medical and Dentistry, Department of Gastroenterology and Hepatology, Research Associate, 医学部・歯学部附属病院, 助手 (80359885)
KATO Jun University Hospital of Medical and Dentistry, Department of Gastroenterology and Hepatology, Research Associate, 医学部・歯学部附属病院, 助手 (90379743)
白羽 英則 岡山大学, 医学部・歯学部附属病院, 助手 (40379748)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | liver regeneration / angiogenesis / tumor marker |
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| Research Abstract |
In the current study, we investigate the effect of gene transfer in liver regeneration. Gamma-glutamyl carboxylase (GGCX) is known as a rate-limiting enzyme in the conversion of des-gamma-carboxy prothrombin (DCP) into normal prothrombin. DCP stimulated cell proliferative activities 1.5-2.0 fold in Hep3B and SK-Hep-1 cells. This effect was brought through activation of Met-JAK1-STAT3 signaling pathway. Moreover, DCP stimulated human umbilical vein endothelial cells (HUVEC). The cell migrative activity and cell proliferative activity were enhanced 2.2 fold and 1.5 fold, respectively by DCP in HUVEC. This effect was caused by activation of phospholipase-C-γ and erk-MAPK. Variant type of GGCX was cloned from hepatocellular carcinoma cell line by RT-PCR. Introduction of variant type-GGCX cDNA converted DCP-negative cell lines into DCP-producing cells. Introduction of siRNA against GGCX showed same effect as introduction of variant type-GGCX. These cells showed enhanced cell migration and proliferation. In conclusion, introduction of variant type-GGCX and siRNA against GGCX might be an effective strategy to control cell proliferation of hepatocyte and angiogenesis in liver regeneration.
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