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Involvement of RhoA/Rho-kinase pathway in the mechanisms regulating uterine muscle contraction. -Rho-kinase as a possible therapeutic target for prevention of preterm delivery -

Research Project

Project/Area Number 14571559
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOsaka University

Principal Investigator

TAHARA Masahiro  Osaka University, Graduate School of Medicine, professor, 医学系研究科, 助手 (00294091)

Co-Investigator(Kenkyū-buntansha) NISHIO Yukihiro  Osaka University, Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (30303952)
TAKEDA Takashi  Osaka University, Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (20301260)
TASAJA Keiichi  Osaka University, Graduate School of Medicine, Associate professor, 医学系研究科, 助教授 (50155058)
MINEKAWA Ryoko  Osaka University Hospital, Assistant professor, 医学部附属病院, 助手 (10359838)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsRhoA / Rho-kinase / Y-27632 / chorioamnionitis / preterm delivery / cervical ripening / RhoA
Research Abstract

We have been focusing on the involvement of RhoAIRho-kinase pathway in the mechanisms regulating uterine muscle contraction. Chorioamnionitis is known to be closely related to preterm delivery, and intrauterine infection has been thought to play a critical role in the pathogenesis of preterm delivery. Lipopolysaccharide cell-surface component of gram-negative organisms, and is elevated in the amniotic fluid of chorioamnionitis. Our data demonstrated that (1) a Rho-kinase inhibitor significanfly reduced the preterm delivery rate in a mouse model of lipopolysaccharide (LPS)-induced preterm delivery, (2) LPS or prostaglandin F2a increased the level of GTP-bound RhoA, and (3) LPS also accelerates the cervical ripening in mice by causing inflammation in the cervix with an influx of polymorphonuclear (PMN) leukocytes, while a Rho-kinase inhibitor significantly inhibited PMN leukocyte infiltration during cervical ripening in an in vivo animal model. These results suggested that Rho-kinase could be used as a new therapeutic target for prevention of preterm labor or premature cervical ripening. We are now investigating the regulation of RhoAIRho-kinase expression in pregnant uterus by sex-steroid hormone to clarify biochemical mechanisms underlying uterine smooth muscle contractility.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Tahara, M., et al.: "RhoA/Rho-kinase cascade is involved in oxytocin-induced rat uterine contraction."Endocrinology. 143(3). 920-929 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawada, K., et al.: "Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of Rho."Cancer Res. 62(21). 6015-6020 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawada, K., et al.: "Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells."Gynecol Oncol. 87(3). 252-259 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tahara, M., Morishige, K., Sawada, K., Ikebuchi, Y., Kawagishi, R., Tasaka, K., Murata, Y.: "RhoA/Rho-kinase cascade is involved in oxytocin-induced rat uterine contraction."Endocrinology. 143. 920-929 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawada, K., Morishige, K., Tahara, M., Kawagishi, R., Ikebuchi, Y., Tasaka, K., Murata, Y.: "Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of rho."Cancer Res. 62. 6015-6020 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sawada, K., Morishige, K., Tahara, M., Ikebuchi, Y., Kawagishi, R., Tasaka, K., Murata, Y.: "Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells."Gynecol Oncol. 87. 252-259 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tahara, M., et al.: "RhoA/Rho-kinase cascade is involved in oxytocin-induced rat uterine contraction"Endocrinology. 143(3). 920-929 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sawada, K., et al.: "Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of rho"Cancer Res. 62(21). 6015-6020 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sawada, K., et al.: "Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells"Gynecol Oncol. 87(3). 252-259 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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