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Physiological role of lysophosphatidic acid.

Research Project

Project/Area Number 15370052
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

AOKI Junken  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学系研究科, 助教授 (20250219)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2003: ¥9,500,000 (Direct Cost: ¥9,500,000)
Keywordslysophosphatidic acid / LPA3 / implantation / knockout mice / prostaglandin / リゾホスファチジン酸受容体 / オートタキシン / autotaxin / がん / 浸潤・転移
Research Abstract

Every successful pregnancy requires proper embryo implantation. (a process of particular importance) Poor implantation rate is a major problem during infertility treatments using assisted reproductive technologies (ART). We report a new molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA_3/edg7. Targeted deletion of LPA_3 resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to embryo death or delayed embryonic development and hypertrophic placentas shared by multiple embryos. An enzyme demonstrated to influence implantation, cyclooxygenase-2 (COX-2), was down-regulated in LPA_3-deficient uteri during preimplantation. COX-2 produces prostaglandins that are critical for implantation ^1, and exogenous administration of the prostaglandins PGE_2 and cPGI into LPA_3-deficient females rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA_3 receptor-mediated signaling as a new influence on implantation and further indicate linkage between LPA signalling and prostaglandin biosynthesis.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (23 results)

All 2005 2004 Other

All Journal Article (17 results) Publications (6 results)

  • [Journal Article] LPA3-mediated lysophosphatidic acid signalling in implantation and embryo spacing2005

    • Author(s)
      Xe, Y.et al.
    • Journal Title

      Nature 435

      Pages: 104-108

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] LPA3-mediated lysophosphatidic acid signalling in implantation.and embryo spacing2005

    • Author(s)
      Tomokazu Amano, Grace Kennedy, Hiroyuki Arai, Junken Aoki, Jerald Chun
    • Journal Title

      Nature 435

      Pages: 104-108

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA12004

    • Author(s)
      Hama, K. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 17634-17639

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identifying Specific Conformations by Using a Carbohydrate Scaffold : Discovery of Subtype-Selective LPA-Receptor Agonists and an Antagonist2004

    • Author(s)
      Tamaruya, Y. et al.
    • Journal Title

      Angew.Chem.Int.Ed.Engl 43

      Pages: 2834-2837

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanisms of lysophosphatidic acid production2004

    • Author(s)
      Aoki, J.
    • Journal Title

      Semin.Cell Dev.Biol. 15

      Pages: 477-489

    • NAID

      10011214554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in C.elegans2004

    • Author(s)
      Inoue, T. et al.
    • Journal Title

      Proc.Natl.Acad.Sci. 101

      Pages: 13233-13238

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma2004

    • Author(s)
      Tanaka, M. et al.
    • Journal Title

      FEBS Lett 571

      Pages: 197-204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in C.elegans2004

    • Author(s)
      Takao Inoue, Asako Sugimoto, Yuka Suzuki, Masayuki Yamamoto, Masafumi Tsujimoto, Junken Aoki, Hiroyuki Arai
    • Journal Title

      Proc.Natl.Acad.Sci. 101

      Pages: 13233-13238

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanisms of lysophosphatidic acid production (review).2004

    • Author(s)
      Junken Aoki
    • Journal Title

      Semin.Cell Dev.Biol. 15

      Pages: 477-489

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostatic acid Phosphatase Degrades Lysophosphatidic Acid in Seminal Plasma2004

    • Author(s)
      Masayuki Tanaka, Yasuhiro Kishi, Yasukazu Takanezawa, Yoshiyuki Kakehi, Junken Aoki, Hiroyuki Arai
    • Journal Title

      FEBS Lett. 571

      Pages: 197-204

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identifying Specific Conformations by Using a Carbohydrate Scaffold : Discovery of Subtype-Selective LPA-Receptor Agonists and an Antagonist.2004

    • Author(s)
      Tamaruya Y, Suzuki M, Kamura G, Kanai M, Hama K, Shimizu K, Aoki J, Arai H, Shibasaki M.
    • Journal Title

      Angew.Chem.Int.Ed.Engl. 43

      Pages: 2834-2837

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1.2004

    • Author(s)
      Hama K, Aoki J, Fukaya M, Kishi Y, Sakai T, Suzuki R, Ohta H, Yamori T, Watanabe M, Chun J, Arai H.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 17634-17639

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA12004

    • Author(s)
      Hama, K.et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 17634-17639

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identifying Specific Conformations by Using a Carbohydrate Scaffold : Discovery of Subtype-Selective LPA-Receptor Agonists and an Antagonist2004

    • Author(s)
      Tamaruya, Y.et al.
    • Journal Title

      Angew.Chem.Int.Ed.Engl 43

      Pages: 2834-2837

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma2004

    • Author(s)
      Tanaka, M.et al.
    • Journal Title

      FEBS Lett 571

      Pages: 197-204

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in C.elegans2004

    • Author(s)
      Inoue, T.et al.
    • Journal Title

      Proc.Natl.Acad.Sci. 101

      Pages: 13233-13238

    • Related Report
      2004 Annual Research Report
  • [Journal Article] LPA3-mediated lysophosphatidic acid signalling in implantation and embryo spacing

    • Author(s)
      Xe, Y.et al.
    • Journal Title

      Nature (In press)

    • Related Report
      2004 Annual Research Report
  • [Publications] Hama K et al.: "Lysophosphatidic Acid and Autotaxin Stimulate Cell Motility of Neoplastic and Non-neoplastic Cells Through LPAL."J.Biol.Chem.. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshida K et al.: "Vascular remodeling induced by naturally occurring unsaturated lysophosphatidic acid in vivo."Circulation. 108. 1746-1752 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Qian L K et al.: "Synthesis of Migration-Resistant Hydroxyethoxy Analogues of Lysophosphatidic Acid."Org Lett.. 5. 4685-4688 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiramatsu T et al.: "Biochemical and molecular characterization of two phosphatidic acid-selective phospholipase A1s, mPA-PLA1alpha and mPA-PLA1beta."J.Biol.Chem.. 278. 49438-49447 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] R.Gijsbers et al.: "The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site."FEBS Letter. 538. 60-64 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.M.McIntyre et al.: "Identification of an intracellular receptor forlysophosphatidicacid (LPA) : LPA is a transcellular PPAR gamma agonist."Proc.Natl.Acad.Sci.. 100. 131-136 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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