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Prevention of hypertensive disorders of pregnancy and improvement of neonatal outcome by Danger Signal suppression

Research Project

Project/Area Number 19K09829
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionNara Medical University

Principal Investigator

NARUSE Katsuhiko  奈良県立医科大学, 医学部, 講師 (70453165)

Co-Investigator(Kenkyū-buntansha) 常見 泰平  奈良県立医科大学, 医学部附属病院, 研究員 (20599831)
竹田 善紀  奈良県立医科大学, 医学部附属病院, 研究員 (50825239)
中野 和俊  奈良県立医科大学, 医学部附属病院, 研究員 (70805879)
赤坂 珠理晃  奈良県立医科大学, 医学部, 助教 (90526724)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords妊娠高血圧腎症 / 妊娠高血圧症候群 / Danger Signal / 常位胎盤早期剥離 / Danger signal / 早産 / 胎盤 / 脳性麻痺
Outline of Research at the Start

1)妊娠初期浸潤型絨毛細胞と満期胎盤由来の絨毛細胞を用いて、低酸素環境などで培養を行い、亢進する因子を証明する。
2)当科にストックされた妊娠高血圧症候群および正常妊娠の母体血清検体、ならびに新生児科の保存する臍帯血検体を用いて、各種因子の測定を行う。
3)ストレス下にある細胞からRNAを抽出し解析してその変動を検討し、疾患の病態発現の鍵となる下流の因子を見出す。
4)見出された因子について脂肪組織培養系に添加し、その炎症性因子が惹起されるかどうかについて検討する。
5)これら因子を抑制できる薬剤をデータベースから見出す。候補となる薬剤について上記の実験系、動物実験、可能なら発症女性で検討する。

Outline of Final Research Achievements

A manuscript on inflammatory upregulation and suppression by Danger Signal in adipose tissue by tissue culture written by Juria Akasaka, a member, was published during this period. The principal investigator proved the association between the existing background pathology between different phenotypes of hypertensive disorders of pregnancy and placental abruption using big data during this period. And also Naruse had the opportunity to give an educational lecture at the Japanese Society of Nephrology. On the other hand, progress in basic research has been delayed due to the clinical effort caused by the COVID disaster, and will continue in April 2022 when the representative moves to a new location.

Academic Significance and Societal Importance of the Research Achievements

妊娠高血圧症候群が妊娠初期の胎盤着床不全に端を発することが明らかとなり、児に対して胎児発育不全や常位胎盤早期剥離といった重篤な異常をもたらす原因として脂肪組織の炎症が関わる可能性を示し、そこにDanger Signalが関与していることが事前の仮説通り証明された。他方、本研究期間では発症予知やハイリスク群の発症予防、児の周産期予後改善につながる方策までは開発することが出来なかった。今後の研究にて証明していくための基礎的な知見を提示することができたと考える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2022 2021 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Book (2 results)

  • [Journal Article] Ultrasound screening in gynecological examinations: can we overcome the criticism that it is insufficient and harmful?2022

    • Author(s)
      Naruse Katsuhiko
    • Journal Title

      Journal of Medical Ultrasonics

      Volume: 49 Issue: 1 Pages: 1-2

    • DOI

      10.1007/s10396-021-01174-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集 症例にマッチする分娩誘発アプローチ HDPに対する分娩誘発2021

    • Author(s)
      成瀬勝彦
    • Journal Title

      産婦人科の実際

      Volume: 70 Pages: 391-395

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Placental abruption in each hypertensive disorders of pregnancy phenotype: a retrospective cohort study using a national inpatient database in Japan2020

    • Author(s)
      Naruse Katsuhiko、for the Advanced Life Support in Obstetrics (ALSO)-Japan Research Group、Shigemi Daisuke、Hashiguchi Mikio、Imamura Masatoshi、Yasunaga Hideo、Arai Takanari
    • Journal Title

      Hypertension Research

      Volume: 44 Issue: 2 Pages: 232-238

    • DOI

      10.1038/s41440-020-00537-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of Receptor for Advanced Glycation Endproducts in Hypertensive Disorders of Pregnancy2019

    • Author(s)
      Akasaka、Naruse、Sado、Uchiyama、Makino、Yamauchi、Ota、Sakuramoto-Tsuchida、Itaya-Hironaka、Takasawa、Kobayashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 21 Pages: 5462-5462

    • DOI

      10.3390/ijms20215462

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Adipokine / Lipokine and inflammatory process in preeclampsia.2021

    • Author(s)
      Naruse K, Akasaka J, Ichikawa M
    • Organizer
      22th World Congress meeting of the International Society for the Study of Hypertension in Pregnancy (ISSHP)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Early onset hypertensive disorders of pregnancy is a high risk phenotype for placental abruption: A Japanese nationwide cohort study.2021

    • Author(s)
      Naruse K, Shigemi D, Hashiguchi M, Imamura M, Yasunaga H, Arai T, for the Advanced Life Support in Obstetrics (ALSO)-Japan Research Group
    • Organizer
      22th World Congress meeting of the International Society for the Study of Hypertension in Pregnancy (ISSHP)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 特別連続企画 胎生期からのライフステージによる病態リスクと対策 妊娠高血圧症候群と腎臓~生涯にわたる影響~2021

    • Author(s)
      成瀬勝彦
    • Organizer
      第64回日本腎臓学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 臓器温存戦略における超音波:産婦人科、主に周産期救急の視点から.2021

    • Author(s)
      成瀬勝彦,赤坂珠理晃,市川麻祐子,三宅龍太,長安実加,大西俊介,竹田善紀,山中彰一郞,木村文則
    • Organizer
      日本超音波医学会第48回関西地方会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 妊娠高血圧症候群と薬物療法2021

    • Author(s)
      成瀬勝彦
    • Organizer
      第9回関西妊産婦薬物療法支援講習会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Book] 妊娠高血圧症候群の診療指針20212021

    • Author(s)
      日本妊娠高血圧学会
    • Total Pages
      264
    • Publisher
      メジカルビュー社
    • ISBN
      9784758321297
    • Related Report
      2021 Annual Research Report
  • [Book] 妊娠期の正常と異常2020

    • Author(s)
      藤井知行、永松健(編)、成瀬勝彦(各章分担執筆)
    • Total Pages
      392
    • Publisher
      中山書店
    • ISBN
      9784521747620
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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