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The molecular mechanism of progesterone signaling to modulate cervical remodeling

Research Project

Project/Area Number 24592488
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNippon Medical School

Principal Investigator

KUWABARA Yoshimitsu  日本医科大学, 医学部, 准教授 (40373013)

Co-Investigator(Kenkyū-buntansha) KATAYAMA Akira  日本医科大学, 医学部, 助教 (10333113)
NAKAI Akihito  日本医科大学, 医学部, 教授 (20227721)
KAWABATA Ikuno  日本医科大学, 医学部, 講師 (20328793)
TAKESHITA Toshiyuki  日本医科大学, 大学院医学研究科, 教授 (60188175)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsプロゲステロン / 早産予防 / 子宮頸管 / 頸管リモデリング / 頸管熟化 / 細胞外マトリクス
Outline of Final Research Achievements

Human uterine cervical fibroblast culture system was established from clinical specimens. Subsequently to the subculture in the medium containing beta-estradiol, expression dynamics of IL-6, IL-8, IL-1beta, PTGS2 and MMPs were assessed by real-time RT-PCR analysis.
LPS (2.0μg/ml) stimulation induced a significant increase of transcript levels of all molecules, which were significantly suppressed by progesterone (P4)(1.0μM)treatment except for IL-6, IL-8. On the other hand, the effect of stimulation with lower concentration of LPS (0.2μg/ml) was suppressed by P4 treatment in all molecules. Furthermore, the suppression was pronounced by the pretreatment of P4 1 hour before LPS stimulation.
Progesterone inhibit the expression of molecules related with preterm labor in a transcript level, and the timing of treatment is considered important in a clinical use to prevent preterm birth.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (5 results)

All 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results)

  • [Journal Article] Progesterone transcriptionally inhibits LPS-induced matrix metalloproteinase up-regulation in human cervical fibroblast cells2014

    • Author(s)
      Y. Kuwabaracorrespondence, A. Katayama, S. Kurihara, M. Yonezawa, N. Ouchi, R. Sawa, T. Takeshita
    • Journal Title

      Journal of Reproductive Immunology

      Volume: 106 Pages: 16-17

    • DOI

      10.1016/j.jri.2014.09.040

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] 培養ヒト子宮頸部線維芽細胞におけるLPS誘導性分子動態に対するプロゲステロンの効果2015

    • Author(s)
      桑原慶充, 杉田洋佑, 内山美穂子, 白井有香, 中尾仁彦,  米澤美令, 大内望, 澤倫太郎, 中井章人, 竹下俊行
    • Organizer
      日本産科婦人科学会 学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-09 – 2015-04-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] The effects of progesterone on the gene expression profile of LPS- stimulated cultured human cervical fibroblasts2015

    • Author(s)
      Yoshimitsu Kuwabara, Akira Katayama, Sachiko Kurihara, Yosuke Sugita, Yuka Shirai, Kimihiko Nakao, Mirei Yonezawa, Nozomi Ouch1, Rintaro Sawa, Toshiyuki Takeshita
    • Organizer
      Society for Reproductive Investigation
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] プロゲステロンはヒト子宮頸部線維芽細胞培養系において、LPS誘導性MMP群の発現を転写レベルで抑制する2014

    • Author(s)
      桑原慶充, 片山映, 米澤美令, 大内望, 澤倫太郎, 中井章人, 竹下俊行
    • Organizer
      日本生殖免疫学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-12 – 2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] プロゲステロンは、ヒト子宮頚部線維芽細胞培養系においてTLR4誘導性のMMP群の発現を転写レベルで抑制する2014

    • Author(s)
      桑原慶充, 米澤美令, 渡邉建一郎, 小野修一, 大内望, 澤倫太郎, 中井章人, 竹下俊行
    • Organizer
      第50回日本周産期・新生児医学会学術集会2014
    • Place of Presentation
      舞浜
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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