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A new therapeutic approach of preeclampsia with lysophospholipids

Research Project

Project/Area Number 23791825
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionNagoya University

Principal Investigator

KOTANI Tomomi  名古屋大学, 医学部附属病院, 講師 (70359751)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords胎児発育不全 / 絨毛浸潤 / S1P / LPA / EVT / 卵膜 / S1P / LPA / EVT / 浸潤 / autotaxin
Research Abstract

The subtypes of receptors of lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) were expressed in EVT at early gestation. LPA3, S1P1 and S1P3 promoted migration of EVT, but S1P2 suppressed that in EVT cell lines. LPA induced invasion of EVT via activation of ERK, STAT-3, and Akt. S1P1 and S1P3 induced the expression of MMP-9, but S1P2 reduced it. The expression pattern of S1PR subtypes was dependent on cell density. In high cell concentration, S1P2 was mainly expressed, but S1P1 and S1P3 were dominantly expressed in low cell concentration. The antagonist of S1P2 (JTE-013) significantly induced migration of EVT. In pregnant ICR mouse, peritoneal injection of JTE-013 had no effect on the development of placenta and fetus, but injection of FTY720 (S1P1 and 3 antagonist) significantly reduced the weight of placenta and fetus, compared with control. Thus, antagonists or agonists of LPA or S1P could be a new therapeutic drug for fetal growth retardation, and preeclampsia.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (21 results)

All 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 9 results) Presentation (10 results) Remarks (1 results)

  • [Journal Article] Altered expression of enzymes regulating the activity of endothelin-1 in the lower segment of the human amnion during labor2013

    • Author(s)
      Kotani T, Iwase A, Tsuda H, et al (他8名)
    • Journal Title

      Biol Reprod

      Volume: 89(3) Pages: 52-52

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased expression of sphingosine kinase in the amnion during labor2013

    • Author(s)
      Erkhembaatar LO, Kotani T, Sumigama S, et al (他9名)
    • Journal Title

      Placenta

      Volume: 34(4) Pages: 353-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 胎児発育不全と胎盤2013

    • Author(s)
      小谷友美, 炭竈誠二, 津田弘之ら(他3名)
    • Journal Title

      産婦人科の実際

      Volume: Vol.62 (8) Pages: 1065-1072

    • Related Report
      2013 Final Research Report
  • [Journal Article] Altered expression of enzymes regulating the activity of endothelin-1 in the lower segment of the human amnion during labor.2013

    • Author(s)
      Kotani T, Iwase A, Tsuda H, Mano Y, Yamamoto E, Nakano T, Hasegawa Y, Li H, Sumigama S, Itakura A, Kikkawa F.
    • Journal Title

      Biok Reprod

      Volume: 89 Issue: 3 Pages: 1-7

    • DOI

      10.1095/biolreprod.113.108480

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased expression of sphingosine kinase in the amnion during labor.2013

    • Author(s)
      Erkhembaatar LO, Kotani T, Sumigama S, Tsuda H, Mano Y, Hua L, Hasegawa Y, Wang J, Sugiyama C, Nakahara T, Iwase A, Kikkawa F.
    • Journal Title

      Placneta

      Volume: 34 Pages: 353-359

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] High expression of N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma2012

    • Author(s)
      Niimi K, Yamamoto E, Kotani T, et al (他7名)
    • Journal Title

      Br J Cancer

      Volume: 107(12) Pages: 1969-77

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A case report of placental mesenchymal dysplasia with an increased VEGF-D expression2012

    • Author(s)
      Kotani T, Sumigama S, Tsuda H, et al (他9名)
    • Journal Title

      Placenta

      Volume: 33(10) Pages: 888-91

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The loss of endoglin promotes the invasion of extravillous trophoblasts2011

    • Author(s)
      Mano Y, Kotani T, Shibata K, et al (他7名)
    • Journal Title

      Endocrinology

      Volume: 152(11) Pages: 4386-94

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The loss of endoglin promotes the invasion of extravillous trophoblasts.2011

    • Author(s)
      Mano Y, Kotani T, Shibata K, Matsumura H, Tsuda H, Sumigama S, Yamamoto E, Iwase A, Senga T, Kikkawa F.
    • Journal Title

      Endocrinology.

      Volume: 152 Pages: 4386-4394

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Maternal mental disorders and pregnancy outcomes: a clinical study in a Japanese population.2011

    • Author(s)
      Hironaka M, Kotani T, Sumigama S, Tsuda H, Mano Y, Hayakawa H, Tanaka S, Ozaki N, Tamakoshi K, Kikkawa F.
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 37 Issue: 10 Pages: 1283-1289

    • DOI

      10.1111/j.1447-0756.2010.01512.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 炎症に起因する早産におけるエンドセリン(ET)-1を制御する酵素の発現バランスについて2014

    • Author(s)
      小谷友美ら(他10名)
    • Organizer
      第66回日本産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
      2014-04-20
    • Related Report
      2013 Final Research Report
  • [Presentation] The new insights of preterm labor with chorioaminonitis(CAM)2014

    • Author(s)
      Tomomi Kotani et al. (他7名)
    • Organizer
      2014 SGI 61^<st> Annual Scientific meeting
    • Place of Presentation
      イタリア、フィレンチェ
    • Year and Date
      2014-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] 炎症に起因する早産におけるエンドセリン(ET)-1を制御する酵素の発現バランスについて2014

    • Author(s)
      小谷友美、炭竈誠二、津田弘之、眞野由紀雄、中野知子、今井健史、諸井博明、
    • Organizer
      第66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(千代田区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The new insights of preterm labor with chorioamnionitis (CAM)2014

    • Author(s)
      Tomomi Kotani, Seiji Sumigama, Hiroyuki Tsuda, Yukio Mano, Tomoko Nakano, Shima Hirako, Hua Li, Fumitaka Kikkawa
    • Organizer
      2014 SGI 61st Annual Scientific Meeting
    • Place of Presentation
      フィレンツェ(イタリア)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The involvement of enzymes which activate and inactivate endothelin-1 (ET-1) in human labor onset2012

    • Author(s)
      Tomomi Kotani, Seiji Sumigama, Hiroyuki Tsuda, Yukio Mano, Tomoko Nakano, Kaoru Nimi, Sawako Fujiwara, Satoshi Matsukawa, Yuriko Watanabe, Li Hua, Fumitaka Kikkawa
    • Organizer
      IFPA2012
    • Place of Presentation
      広島
    • Related Report
      2012 Research-status Report
  • [Presentation] The new mediators of human labour-onset2012

    • Author(s)
      Tomomi Kotani, Tomoko Nakano, Yuriko Watanabe, Yukio Mano, Hiroyuki Tsuda, Li hua,
    • Organizer
      COGI
    • Place of Presentation
      リスボン
    • Related Report
      2012 Research-status Report
  • [Presentation] 絨毛浸潤の調節について2011

    • Author(s)
      小谷友美ら(他7名)
    • Organizer
      第19回日本胎盤学会学術集会
    • Place of Presentation
      東京ステーションコンファレンス(東京都千代田区)
    • Year and Date
      2011-10-01
    • Related Report
      2013 Final Research Report
  • [Presentation] リゾリン脂質による絨毛浸潤機能の調節作用2011

    • Author(s)
      小谷友美ら(他10名)
    • Organizer
      第63回日本産婦人科学会学術講演会
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Year and Date
      2011-08-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 絨毛浸潤の調節について

    • Author(s)
      小谷友美
    • Organizer
      第19回日本胎盤学会学術集会
    • Place of Presentation
      東京ステーションコンファレンス
    • Related Report
      2011 Research-status Report
  • [Presentation] リゾリン脂質による絨毛浸潤機能の調節作用

    • Author(s)
      小谷友美
    • Organizer
      第63回日本産婦人科学会学術講演会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.med.nagoya-u.ac.jp/obgy/research/obstetrics/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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