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Gene network analysis of placental function regulators and a seed gene, ezrin

Research Project

Project/Area Number 25860396
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionKeio University

Principal Investigator

NISHIMURA Tomohiro  慶應義塾大学, 薬学部, 講師 (40453518)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords胎児発育不全 / 血液胎盤関門 / 遺伝子ネットワーク / 胎児成長不全 / エズリン / ヒポタウリン / 遺伝子ネットワーク解析 / トランスポーター / 胎盤
Outline of Final Research Achievements

Placental function plays important roles in the fetal growth. Ezrin is a regulatory gene for plasma membrane proteins in the placenta, and deficiency of ezrin induces fetal growth retardation (FGR). This study aimed to clarify a gene network between ezrin and the other genes responsible for FGR by means of informatics and experiments in order to understand the molecular mechanism of the ezrin-mediated FGR. Network analysis showed no direct relationship between ezrin and the known FGR-related genes, indicating that ezrin-mediated FGR includes the novel molecular mechanism. We further analyzed protein interaction between Ezrin and a hypotaurine transporter, SLC6A13 in the placenta, since Ezrin knockout fetal mice showed deficiency of hypotaurine. Ezrin and SLC6A13 are co-localized on the plasma membrane in the labyrinth zone of mouse placenta. These results indicate that a novel interaction between Ezrin and SLC6A13 is important for fetal growth.

Report

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

    (15 results)

All 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (8 results)

  • [Journal Article] Organic anion transporter 4-mediated transport of olmesartan at basal plasma membrane of human placental barrier2015

    • Author(s)
      Noguchi S, Nishimura T, Fujibayashi A, Maruyama T, Tomi M, Nakashima E.
    • Journal Title

      J Pharm Sci

      Volume: 104 Issue: 9 Pages: 3128-3135

    • DOI

      10.1002/jps.24434

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts2015

    • Author(s)
      Nishimura T, Duereh M, Sugita Y, Yoshida Y, Higuchi K, Tomi M, Nakashima E.
    • Journal Title

      Placenta

      Volume: 36 Issue: 6 Pages: 693-698

    • DOI

      10.1016/j.placenta.2015.02.014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Fetal growth retardation and lack of hypotaurine in ezrin knockout mice2014

    • Author(s)
      Nishimura T, Higuchi K, Sai Y, Sugita Y, Yoshida Y, Tomi M, Wada M, Wakayama T, Tamura A, Tsukita S, Soga T, Nakashima E.
    • Journal Title

      PLoS ONE

      Volume: 9 Issue: 8 Pages: e105423-e105423

    • DOI

      10.1371/journal.pone.0105423

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of protein kinase A in regulating steroid sulfate uptake for estrogen production in human placental choriocarcinoma cells2014

    • Author(s)
      Tomi M, Miyata Y, Noguchi S, Nishimura S, Nishimura T, Nakashima E.
    • Journal Title

      Placenta

      Volume: 35 Issue: 8 Pages: 658-660

    • DOI

      10.1016/j.placenta.2014.06.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] System amino acid transporter SNAT2 shows subtype-specific affinity for betaine and hyperosmotic inducibility in placental trophoblasts.2014

    • Author(s)
      Nishimura T, Yagi R, Usuda M, Oda K, Yamazaki M, Suda S, Takahashi Y, Okazaki F, Sai Y, Higuchi, K, Maruyama T, Tomi M, Nakashima E
    • Journal Title

      Biochim Biophys Acta.

      Volume: VOL. 1838 Issue: 5 Pages: 1306-12

    • DOI

      10.1016/j.bbamem.2014.01.004

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of rat in vivo fetal-to-maternal transfer clearances of various xenobiotics by umbilical perfusion.2013

    • Author(s)
      Nishimura T, Takanohashi T, Tomi M, Horikoshi M, Higuchi K, Sai Y, Nakashima E.
    • Journal Title

      J Pharm Sci

      Volume: 102(9) Issue: 9 Pages: 3356-3363

    • DOI

      10.1002/jps.23551

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Estrogen receptor α induction by mitoxantrone increases Abcg2 expression in placental trophoblast cells.2013

    • Author(s)
      Oda K, Nishimura T, Higuchi K, Ishido N, Ochi K, Iizasa H, Sai Y, Tomi M, Nakashima E.
    • Journal Title

      J Pharm Sci

      Volume: 102 Issue: 9 Pages: 3364-3372

    • DOI

      10.1002/jps.23549

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Distribution of hypotaurine transporter, Slc6a13, in placental trophoblasts during mid to late pregnancy2014

    • Author(s)
      Nishimura T, Araki H, Takaki Y, Tomi M, Nakashima E
    • Organizer
      19th North American ISSX Meeting / 29th JSSX Meeting
    • Place of Presentation
      San Francisco
    • Year and Date
      2014-10-19 – 2014-10-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Slc6a13の胎盤における発現分布とヒポタウリン取込み輸送による酸化ストレスからの細胞保護2014

    • Author(s)
      西村友宏、小島和晃、高木良也、荒木光、登美斉俊、中島恵美
    • Organizer
      第9回トランスポーター研究会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-06-14 – 2014-06-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒポタウリントランスポーターSlc6a13の胎盤における発現と細胞保護作用2014

    • Author(s)
      西村 友宏、荒木 光、小島 和晃、登美 斉俊、中島 恵美
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hypotaurine transporter contributes to cytoprotection in placental trophoblasts from oxidative stress2014

    • Author(s)
      Nishimura T, Tomi M, Nakashima E
    • Organizer
      5th Asia Pasific International Society for the Study of Xenoiotics (ISSX) Meeting
    • Place of Presentation
      Tienjin
    • Year and Date
      2014-05-09 – 2014-05-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cytoprotective properties of hypotaurine by scavenging hydroxyl radicals in placental trophoblast cells.2013

    • Author(s)
      Araki H, Duereh M, Nishimura T, Sugita Y, Higuchi K, Tomi M, Nakashima E.
    • Organizer
      International Federation of Placenta Associations(IFPA)2013
    • Place of Presentation
      Whistler, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Rat in vivo fetal-to-maternal transfer clearances of various xenobiotics by umbilical perfusion.2013

    • Author(s)
      Nishimura T, Tomi M, Nakashima E.
    • Organizer
      International Society for the Study of Xenobiotics, 10th International ISSX Meeting
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2013 Research-status Report
  • [Presentation] Uptake and antioxidative effect of hypotaurine in the placenta.2013

    • Author(s)
      Araki H, Duereh M, Sugita Y, Higuchi K, Nishimura T, Tomi M, Nakashima E.
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2013
    • Place of Presentation
      Jeju, Republic of Korea
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒポタウリンの胎盤での生理的濃度維持における細胞膜輸送の寄与および活性酸素除去作用.2013

    • Author(s)
      西村友宏、杉田友紀、Mariam Duereh、登美斉俊、中島恵美.
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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