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Regulatory mechanism of microenvironment at fetomaternal interface by lipid mediators and progesterone

Research Project

Project/Area Number 15H04979
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionThe University of Tokyo

Principal Investigator

Fujii Tomoyuki  東京大学, 医学部附属病院, 教授 (40209010)

Co-Investigator(Kenkyū-buntansha) 廣田 泰  東京大学, 医学部附属病院, 講師 (40598653)
永松 健  東京大学, 医学部附属病院, 准教授 (60463858)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2015: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywords脂質メディエーター / 胎盤 / 妊娠高血圧症候群 / リゾホスファチジン酸 / 子宮内膜 / プロゲステロン / 着床 / 微小環境 / 絨毛細胞 / 妊娠 / リゾリン脂質 / 周産期 / 脂質 / 胎盤形成
Outline of Final Research Achievements

The involvement of lysophosphatidic acid (LPA) signaling pathway in the regulation of trophoblast cell activities and placental function was investigated. We found that the serum level of autotaxin (ATX), a secretory enzyme essential for LPA production was remarkably elevated in pregnant women and that the placenta was a major source of ATX. In-vitro study revealed that LPA signaling induced the expression of the genes related to angiogenesis, immune modulation and cell differentiation in trophoblast cells. Abnormal expression pattern of the molecules associated with LPA signaling was observed in the placentas complicated with preeclampsia and fetal growth restriction, suggesting the relevance of deranged LPA signaling to pathoetiology of those diseases. Our findings propose that LPA signaling pathway can be a therapeutic target for preeclampsia and recurrent pregnancy loss.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (16 results)

All 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Invited: 1 results)

  • [Journal Article] A Rho-associated coiled-coil containing kinases (ROCK) inhibitor, Y-27632, enhances adhesion, viability and differentiation of human term placenta-derived trophoblasts in vitro2017

    • Author(s)
      Kenichiro Motomura, Naoko Okada, Hideaki Morita, Mariko Hara, Masato Tamari, Keisuke Orimo, Go Matsuda, Ken-Ichi Imadome, Akio Matsuda, Takeshi Nagamatsu, Mikiya Fujieda, Haruhiko Sago, Hirohisa Saito, and Kenji Matsumoto
    • Journal Title

      PLOS ONE

      Volume: in press Issue: 5 Pages: e0177994-e0177994

    • DOI

      10.1371/journal.pone.0177994

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Adenomyosis and adverse perinatal outcomes: increased risk of second trimester miscarriage, preeclampsia, and placental malposition2017

    • Author(s)
      Hashimoto A, Iriyama T, Sayama S, Nakayama T, Komatsu A, Miyauchi A, Nishii O, Nagamatsu T, Osuga Y, Fujii T1
    • Journal Title

      J Mater Fetal Neonata Med

      Volume: 31 Issue: 3 Pages: 364

    • DOI

      10.1080/14767058.2017.1285895

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autotaxin–lysophosphatidic acid–LPA<sub>3</sub> signaling at the embryo-epithelial boundary controls decidualization pathways2017

    • Author(s)
      Aikawa Shizu、Kano Kuniyuki、Inoue Asuka、Wang Jiao、Saigusa Daisuke、Nagamatsu Takeshi、Hirota Yasushi、Fujii Tomoyuki、Tsuchiya Soken、Taketomi Yoshitaka、Sugimoto Yukihiko、Murakami Makoto、Arita Makoto、Kurano Makoto、Ikeda Hitoshi、Yatomi Yutaka、Chun Jerold、Aoki Junken
    • Journal Title

      EMBO J

      Volume: 36 Issue: 14 Pages: 2146

    • DOI

      10.15252/embj.201696290

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor2017

    • Author(s)
      Fujii Tatsuya、Nagamatsu Takeshi、Morita Kazuki、Schust Danny J.、Iriyama Takayuki、Komatsu Atsushi、Osuga Yutaka、Fujii Tomoyuki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12455-12455

    • DOI

      10.1038/s41598-017-12685-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 妊娠高血圧症候群の新知見 Preeclampsiaの胎盤機能障害 リゾリン脂質シグナルシステムからの視点2016

    • Author(s)
      永松 健
    • Journal Title

      日本周産期・新生児医学会雑誌

      Volume: 52 Pages: 434-434

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Placental autotaxin expression is diminished in women with pre-eclampsia2015

    • Author(s)
      Ichikawa M, Nagamatsu T, Schust DJ, Kawai-Iwasawa Y, Kawana K, Yamashita T, Osuga Y, Aoki J, Yatomi Y, Fujii T
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 41 Issue: 9 Pages: 1406-11

    • DOI

      10.1111/jog.12742

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] Enhanced LPA-LPAR3 signaling under high oxidative stress environment in human placenta and its relevance to the pathoetiology of preeclampsia.2017

    • Author(s)
      Tatsuya Fujii, Takeshi Nagamatsu, Mayuko Ichiikawa-Matsubara, Takayuki Iriyama, Atsushi Komatsu, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
    • Organizer
      第69回日本産科婦人科学会学術講演会
    • Place of Presentation
      広島、広島
    • Year and Date
      2017-04-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 末梢血オートタキシン濃度は胎盤機能を反映する.2017

    • Author(s)
      西森 裕美子, 永松 健, 藤井 知行,他:
    • Organizer
      日本生殖免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] LPAR3 signaling is possibly involved in the clearance of oxidative stress in preeclamptic placenta.2017

    • Author(s)
      Fujii T, Nagamatsu T,他,
    • Organizer
      日本産科婦人科学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] LPA-LPAR3システムの障害から見たPreeclampsiaの病態機序の解明2016

    • Author(s)
      藤井達也 永松健 市川麻祐子 河合有希 川名敬 大須賀穣 藤井知行
    • Organizer
      第31回日本生殖免疫学会総会・学術集会
    • Place of Presentation
      神戸、兵庫
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Preeclampsiaの胎盤機能障害-リゾリン脂質シグナルシステムからの視点2016

    • Author(s)
      永松 健
    • Organizer
      第52回日本周産期新生児医学会学術集会 シンポジウム
    • Place of Presentation
      富山、富山
    • Year and Date
      2016-07-16
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Preeclampsiaの胎盤機能障害-リゾリン脂質シグナルシステムからの視点2016

    • Author(s)
      永松 健
    • Organizer
      第52回 日本周産期新生児医学会学術集会
    • Place of Presentation
      富山国際会議場・富山県民会館・ANAクラウンプラザホテル富山・富山市民プラザ(富山県・富山市)
    • Year and Date
      2016-07-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Enhanced expression of LPARs in preeclamptic placentas2016

    • Author(s)
      Tatsuya Fujii, Takeshi Nagamatsu, Mayuko Itikawa-Matsubara, Takayuki Iriyama, Atsushi Komatsu, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
    • Organizer
      第68回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京、東京
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Enhanced expression of lysophosphatidic acid receptors in preeclamptic placentas2016

    • Author(s)
      Atsushi Komatsu, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
    • Organizer
      第68回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2016-04-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 妊娠子宮の炎症制御におけるマクロファージの関与2015

    • Author(s)
      永松 健
    • Organizer
      第30回日本生殖免疫学会
    • Place of Presentation
      くまもと県民交流館パレア(熊本県・熊本市)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Alteration of LPA signaling in preeclamptic placenta2015

    • Author(s)
      Tatsuya Fujii, Takeshi Nagamatsu, Mayuko Ichiikawa-Matsubara, Yuki Kawai-Iwasawa, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
    • Organizer
      12th World Congress of Perinatal Medicine
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      2015-11-03
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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