2003 Fiscal Year Final Research Report Summary
Functional Analysis of The Biological Activities of a Lipid Mediator, Lysophoshatidie Acid, on The Pathogenesis of Liver Fibrosis
| 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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| Keywords | LYSOPHOSHATIDIC ACID / HEPATIC STELLATE CELLS / AUTOTAXIN / LIPID PHOSPHATE PHOSPHOHYDROLASE |
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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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[Publications] Yanase M., Ikeda H., Matsui A., Noiri E., TOmiya T., Arai M., Inoue Y., Tejima K., Nishikawa T., Kimura S., Fujiwara K., Rojkind M., Ogata I.: "HMG-CoA reductase inhibitor modulates collagen gel-contraction by hepatic myofibroblast-like stellate cell line."Comp. Hepatol.. 3(Suppl 1). S21 (2004)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yanase M, Ikeda H, Ogata I, Matsui A, Noiri E, Tomiya T, Arai M, Inoue Y, Tejima K, Nagashim K, Nishikawa T, Shibata M, Ikebe N, Rojkind M, Fujiwara K.: "Functional Diversity between Rho-kinase-and MLCK-mediated cytoskeletal actions in a myofibroblast-like hepatic stellate cell line."Biochem Biophys Res Commun.. 305. 223-228 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Ikeda H, Nagashima K, Yanase M, Tomiya T, Arai M, Inoue Y, Tejima K, Nishikawa T, Omata M, Kimura S, Fujiwara K.: "Involvement of Rho/Rho-kinase Pathway in Regulatio of Apoptosisin Rat Hepatic Stellate Cells."Am J Physiol Gastrointest Liver Physiol.. 285. G880-G886 (2003)
Description
「研究成果報告書概要(欧文)」より
