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PORTAL HYPERTENSION-ELUCIDATION OF THE MECHANISM IN THE LIGHT OF FUNCTIONAL ABNORMALITIES OF HEPATIC STELLATE CELLS AND DEVELOPMENT OF THERAPEUTIC STRATEGY

Research Project

Project/Area Number 12670461
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

IKEDA Hitoshi  The UNIV. OF TOKYO, FACULTY OF MEDICINE, INSTRUCTOR, 医学部・附属病院, 助手 (80202422)

Co-Investigator(Kenkyū-buntansha) YANASE Mikio  The UNIV. OF TOKYO, FACULTY OF MEDICINE, INSTRUCTOR, 医学部・附属病院, 助手 (50334397)
ARAI Masahiro  The UNIV. OF TOKYO, FACULTY OF MEDICINE, INSTRUCTOR, 医学部・附属病院, 助手 (60271566)
TOMITA Tomoaki  The UNIV. OF TOKYO, FACULTY OF MEDICINE, INSTRUCTOR, 医学部・附属病院, 助手 (90227637)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsPORTAL HYPERTENSION / HEPATIC STELLATE CELLS / SPHINGOSINE 1-PHOSPHATE / LYSOPHOSPHATIDIC ACID / スフィンゴシンコリン酸
Research Abstract

Contractility and mobility of hepatic stellate cells (HSIs) are considered to directly affect portal blood pressure. Effects of sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA), novel lipid mediators, on these cell functions of cultured rat HSCs and roles of these mediators in portal hypertension were investigated. (1) S1P and LPA stimulated contractility of HSCs by activation of Rho and Rho kinase. (2) LPA stimulated mobility of HSCs also by activation of Rho and Rho kinase. (3) Among S1P receptors, mRNA expressions of Edg1 and Edg5 were detected in HSCs. Edg1 and Edg7 were determined in HSCs. Edg7 mRNA expression was decreased in the process or hepatic fibrosis. (5) Addition of S1P or LPA in the solution of the portal perfusion system in the rat liver caused the enhancement of portal pressure. The effect was cancelled in the presence of Y-27632, a specific inhibitor or Rho kinase. Our results indicate that S1P and LPA enhance portal blood pressure by activation of Rho and Rho kinase. These lipid mediators may be involved in the pathogenesis of portal hypertension.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Ikeda H: "Biological activities of a novel lipid mediator sphingosine 1-phosphate, in rat hepatic stellate cells"Am. J. Physiol. 279. G304-G310 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanase M: "Lysophosphatidic acid enhances collagen gel contraction by hepatic stellate cells : Association with Rho-kinase"Biochem. Biophys Res Commun. 277. 72-78 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanase M: "Involvement of Ryo-kinase in lysophosphatic acid-induced migration of hepatic stellate cells"Cells of the Hepatic Sinusoid. 8. 266-268 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikeda H, Yatomi Y, Yanase M, Satoh H, Maekawa H, Ogata I, Ozaki Y, Takuwa Y, Mochida S, and Fujiwara K: "Biological activities of a novel lipid mediator, sphingosine 1-phosphate, in rat hepatic stellate cells"Am. J. Physiol. Gastrointest. Liver Physiol. 279. G304-G310 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanase M, Ikeda H, Matsui A, Maekawa H, Noiri E, Tomiya T, Arai M, Yano T, Shibata M, Ikebe M, Fujiwara K, Rojkind M, and Ogata I: "Lysophosphatidic acid enhances collagen gel contraction by hepatic stellate cells : association with Rho-kinase"Biochem. Biophys. Res. Commun. 277. 72-78 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanase M, Ikeda H, Matsui A, Noiri E, Yano T, Shibata M, Ikebe M, Fujiwara K, and Ogata I: "Involvement of Rho-kinase in lysophosphatic acid-induced migration of hepatic stellate cells"Cells of the Hepatic Sinusoid. vol. 8. 266-268 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikeda H.: "Biological activities of novel lipid mediator, sphingosine 1-phosphate, in rat hepatic stellate cells"Am. J. Physiol.. 279. G304-G310 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yanase M.: "Lysophoshatidic acid enhances collagen gel contraction by hepatic satellite cells : Association with Rho-kinase"Biochem. Biophys. Res. Commun.. 277. 72-78 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yanase M.: "Involvement of Rho-kinase in lysophosphatic acid-induced migration of hepatic stellate cells"Cells of the Hepatic Sinusoid. 8. 266-268 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikeda H.: "Biological activities of a novel lipid mediator, sphingosine l-phosphate, in rat hepatic stellate cells."Am.J.Physiol.. 279. G304-G310 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yanase M.: "hysophosphatidic acid enhances collagen gel contraction by hepatic stellate cells : Association with Rho-kinase."Biochem.Biophys.Res.Commun.. 277. 72-78 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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