| Project/Area Number |
14570448
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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 | The University of Tokyo |
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Principal Investigator |
YANASE Mikio The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (50334397)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Masahiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (60271566)
TOMIYA Tomoaki The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (90227637)
IKEDA Hitoshi The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (80202422)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | LYSOPHOSHATIDIC ACID / HEPATIC STELLATE CELLS / AUTOTAXIN / LIPID PHOSPHATE PHOSPHOHYDROLASE / 低分子量G淡白質Rho / 肝細胞 / Lysophospholipase D / Auto taxin |
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| Research Abstract |
In this research, we focused on the biological function of the lipid mediator, lysophosphatidic acid (LPA)_1 especially on the hepatic stellate cells, the principal components played in the pathogenesis of the liver fibrosis,
Among the three known receptors for LPA, the HSCs ax-pressed primarily LPA_1, and LPA_3 as well, examined by RT-PCR and/or Western blot analysis. DNA synthesis, collagen gel-contractility, and migration elicited by LPA were attenuated when co-added with dioctyiglycerol pyrophosphate (DGPP), a receptor-selective antagonist for LPA_1 and/or LPA_3. DGPP attenuated the LPA-enhanced adhesion of the HSCs to extracellular substrate assessed by the electric cell-substrate impedance sensor. Protein expression of the activated state of the GTPases Rac and RhoA, phosphorylation of the extracellular regulated kinases, and the myosin regulatory light chain were attenuated when co-added with DGPP compared as LPA only. RTPCR transcripts of the LPA-producing lysophospholipase D (Autotaxin) as well as LPA-degradating lipid phosphate phosphohydrolase 1 were detected in the HSCs. These data suggest that LPA exerts its receptor-mediated biological effects in the HSCs, and that the HSCs may regulate LPA biosynthesis and/or degradation by themselves.
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