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Investigation on the molecular mechanism regulating endovascular differentiation of extravillous trophoblast

Research Project

Project/Area Number 18591221
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionKyushu University

Principal Investigator

FUKUSHIMA Kotaro  Kyushu University, Hospital, Assistant Professor (40304779)

Co-Investigator(Kenkyū-buntansha) TSUKIMORI Kiyomi  Kyushu University, Hospital, Assistant Professor (90253450)
浅野間 和夫  九州大学, 大学病院, 助手 (30380413)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,850,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsTrophoblast / Endovascular differentiation / HIFIA / matrigel
Research Abstract

Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis, inducing remodeling of the spiral arteries that increases blood flow toward the intravillous space. We have previously shown that signals involving the vascular endothelial growth factor (VEGF) axis are essential for endovascular differentiation through integrin signaling from the extracellular matrix: This was accomplished with use of the human EVT cell line TCL1, which shows tube formation that specifically recalls morphological changes in endothelial cells.
Tb investigate endovascular differentiation in EVT further, we used DNA microarray analysis to examine the alteration in gene expression profile in TCL1 cells during tube formation on matrigel under normoxia. Hypoxia inducible, factor (HIF)1A, a subunit of HIF1 transcription factor that regulates not only adaptive responses to hypoxia, but also many cellular functions under normoxia, was up-regulated during this morphological change. HIF1A induces VEGF and ITGAV/ITGB3 aggregation, actions known to be important for cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up-regulation using siRNA introduction or chemical inhibition suppressed hypoxia-responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3 aggregation accompanied by the inhibition of tube formation in TCL1 cells.
These results suggest that HIF1A has a crucial role in regulating EVT behavior including matrigel-induced endovascular differentiation under normoxia.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (15 results)

All 2008 2007

All Journal Article (7 results) (of which Peer Reviewed: 2 results) Presentation (8 results)

  • [Journal Article] Hypoxia Inducible Factor 1 Alpha Regulates Matrigel-ind uced Endovascular Differentiation under Normoxia in a Human ExtraviHous Trophoblast Cell Line2008

    • Author(s)
      Fukushima K, et. al.
    • Journal Title

      Placenta (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hypoxia Inducible Factor 1 Alpha Regulates Matrigel-induced Endovascular Differentiation under Normoxia in a Human Extravillous Trophoblast Cell Line2008

    • Author(s)
      Fukushima, K, Murata, M, Hachisuga, M, Tsukimori, K, Kato, K, Seki, H, Takeda, S, Asanoma, K, Wake, N
    • Journal Title

      Placenta (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hypoxia Inducible Factor 1 Alpha Regulates Matrigel-induced Endovascular Diffe rentiation under Normoxia in a Human Extravillous Trophoblast Cell Line2008

    • Author(s)
      Fukushitna K, et. al.
    • Journal Title

      Placenta (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 絨毛細胞の分化機構2007

    • Author(s)
      福嶋 恒太郎, 他
    • Journal Title

      産科と婦人科 74

      Pages: 775-781

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Journal Article] マイクロアレイによる遺伝子発現プロフィール解析 胎盤絨毛細胞の機能分化における検討を一例に2007

    • Author(s)
      福嶋 恒太郎, 他
    • Journal Title

      臨床検査 51

      Pages: 1686-1690

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] マイクロアレイによる遺伝子発現プロフィール解析胎盤絨毛細胞の機能分化における検討を一例に2007

    • Author(s)
      福嶋 恒太郎, 他
    • Journal Title

      臨床検査 51

      Pages: 1686-1690

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 絨毛細胞の分化機構2007

    • Author(s)
      福嶋恒太郎, 浅野間和夫, 和氣徳夫
    • Journal Title

      産科と婦人科 (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Presentation] Investigation on genes involved in the endovascular invasion of human extravillous trophoblast2007

    • Author(s)
      Fukushima K, et. al.
    • Organizer
      The 14th World congress on Gestational Trophoblastic Disease
    • Place of Presentation
      Fukuoka,Japan
    • Year and Date
      2007-11-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Investigation on genes involved in the endovascular invasion of human extravillous trophoblast2007

    • Author(s)
      Fukushima, K, Murata, M, Hachisuga, M, Tsukimori, K, Wake, N
    • Organizer
      The 14th World congress on Gestational Trophoblastic Disease Fukuoka
    • Place of Presentation
      Japan
    • Year and Date
      2007-11-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Investigation on genes involved in the endovascular invasion of human extravillous trophoblast2007

    • Author(s)
      Fukushima K, et. al.
    • Organizer
      The 14^<th> World congress on Gestational Trophoblastic Disease
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2007-11-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] HIFlA IS ESSENTIAL FOR THE ENDOVASCULAR DIFFERNTIATION IN HUMAN EXTRAVILLOUS TROPHOBLAST CELL LINE2007

    • Author(s)
      Fukushima K, et. al.
    • Organizer
      Asian and Oceanic Congress of Obstetrics and Gynecology
    • Place of Presentation
      Tokyo,Japan
    • Year and Date
      2007-09-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] HIFIA S ESSENTLAL FOR THE ENDOVASCULAR DIFFEERNTIATION IN HUMAN EXTRAVILLOUS TROPHOBLAST CELL LINE2007

    • Author(s)
      Fukushima, K, Asanoma, M, Tsukimori, K, Wake, N, Seki, H, Takeda, S
    • Organizer
      Asian and Oceanic Congress of Obstetrics and Gynecology
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2007-09-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] HIF1A IS ESSENTIAL FOR THE ENDOVASCULAR DIFFERNTIATION IN HUMAN EXTRAVILLOUS TROPHOBLAST CELL LINE2007

    • Author(s)
      Fukushima K, et. al.
    • Organizer
      Asian and Oceanic Congress of Obstetrics and Gynecology
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2007-09-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Hypoxia-inducible factor1 alphaは絨毛外トロフォブラストの血管内皮様分化を制御する2007

    • Author(s)
      福嶋 恒太郎, 他
    • Organizer
      第59回日本産科婦人科学会学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2007-04-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Hypoxia-inducible factorl alphaは絨毛外トロフォブラストの血管内皮様分化を制御する2007

    • Author(s)
      福嶋 恒太郎, 他
    • Organizer
      第59回日本産科婦人科学会学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2007-04-16
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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