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The development of new therapy for preeclampsia via modulation of autophagy

Research Project

Project/Area Number 16K11082
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionUniversity of Toyama

Principal Investigator

Nakashima Akitoshi  富山大学, 附属病院, 講師 (00436792)

Co-Investigator(Kenkyū-buntansha) 島 友子  富山大学, 大学院医学薬学研究部(医学), 助教 (00377285)
齋藤 滋  富山大学, 大学院医学薬学研究部(医学), 教授 (30175351)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords妊娠高血圧症候群 / オートファジー / ERストレス / TFEB / 胎盤 / 妊娠高血圧腎症 / 胎児発育遅延 / Atg4B / 胎盤成長因子 / トランスサイレチン / リソソーム / 小胞体ストレス
Outline of Final Research Achievements

There were four tasks that we set up in this study for 3 years. 1) Endoplasmic reticulum stress-inhibited autophagy: The results we obtained for 3 years are submitted to a scientific journal. 2) New approach for activating autophagy via transcriptional factor EB (TFEB), wew transcriptional factor for activating autophagy; part of results are submitted to a scientific journal. 3) VEGF activation via TFEB; The method to evaluate vegf via TFEB modulation are under construction in trophoblast cells. We need some time. 4) New serum marker for severity or onset of preeclampsia; We found a candidate to see that. A correlation between the marker and autopahgic functions in placenta are now investigated. The progress of this study was doning well.

Academic Significance and Societal Importance of the Research Achievements

妊娠高血圧症候群(HDP)は、世界中で約1000万人の妊婦が罹患し、その中で7万6000人の妊婦および50万人の胎児が死亡する疾患である。HDP妊婦(特に早発型,重症)から生まれた新生児は発育が不全となり、多くの神経発達障害を認めるため、HDPは次世代にも悪影響を与える疾患である。高齢妊婦に起こり易いというHDPの疫学的特徴は、高齢化の進む日本でのHDP増加を増加を示唆するが、HDPに有効な治療法はない。今回の新規経路を明らかにすることで、胎盤をターゲットに治療を行うことで、母体・胎児両方を治療できる可能性がある。これは、次世代への福音にもなり得るものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (15 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Book (2 results)

  • [Journal Article] IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery2019

    • Author(s)
      Albrecht Christian、Ichizuka Kiyotake、Nagamatsu Takeshi、Nakashima Akitoshi、Saito Shigeru、O'Tierney-Ginn Perrie
    • Journal Title

      Placenta

      Volume: 18 Pages: 31200-1

    • DOI

      10.1016/j.placenta.2019.02.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trophoblast-Specific Conditional Atg7 Knockout Mice Develop Gestational Hypertension2018

    • Author(s)
      Aoki A, Nakashima A, Kusabiraki T, Ono Y, Yoshino O, Muto M, Kumasawa K, Yoshimori T, Ikawa M, Saito S
    • Journal Title

      Am. J. Pathol.

      Volume: 188 Issue: 11 Pages: 2474-2486

    • DOI

      10.1016/j.ajpath.2018.07.021

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophil Depletion Exacerbates Pregnancy Complications, Including Placental Damage, Induced by Silica Nanoparticles in Mice2018

    • Author(s)
      Higashisaka Kazuma、Nakashima Akitoshi、Iwahara Yuki、Aoki Aiko、Nakayama Masahiro、Yanagihara Itaru、Lin Ying、Nagano Kazuya、Tsunoda Shin-ichi、Saito Shigeru、Yoshioka Yasuo、Tsutsumi Yasuo
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 1850-1850

    • DOI

      10.3389/fimmu.2018.01850

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD11c+ M1-like macrophages (MΦs) but not CD206+ M2-like MΦ are involved in folliculogenesis in mice ovary2018

    • Author(s)
      Ono Yosuke、Nagai Miwako、Yoshino Osamu、Koga Kaori、Nawaz Allah、Hatta Hideki、Nishizono Hirofumi、Izumi Gentaro、Nakashima Akitoshi、Imura Johji、Tobe Kazuyuki、Fujii Tomoyuki、Osuga Yutaka、Saito Shigeru
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 8171-8171

    • DOI

      10.1038/s41598-018-25837-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of autophagy in oocytogenesis, embryogenesis, implantation and pathophysiology of preeclampsia.2017

    • Author(s)
      Nakashima A, Aoki A, Kusabiraki T, Shima T, Yoshino O, Shi-Bin Cheng, Sharma S, Saito S.
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 43 Issue: 4 Pages: 633-643

    • DOI

      10.1111/jog.13292

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Autophagy regulation in preeclampsia: Pros and cons.2017

    • Author(s)
      2.Nakashima A, Aoki A, Kusabiraki T, Cheng SB, Sharma S, Saito S.
    • Journal Title

      Journal of reproductive immunology

      Volume: 123 Pages: 17-23

    • DOI

      10.1016/j.jri.2017.08.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] The role of autophagy in pathophysiology of preeclampsia: Correlation between trophoblast-specific Atg7 knockout-mediated poor placentation and human preeclamptic placentas.2018

    • Author(s)
      AKITOSHI NAKASHIMA
    • Organizer
      38th American-Sino joint meeting of reproductive immunology (ASRI-CSI 2018), Shanghai, China
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Trophoblast-specific Atg7 knockout-mediated poor placentation elicits hypertension, but not proteinuria2018

    • Author(s)
      AKITOSHI NAKASHIMA
    • Organizer
      38th American-Sino joint meeting of reproductive immunology. Shanghai, China.2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of autophagy for pathophysiology of preeclampsia: Correlation between trophoblasts-specific Atg7 knockout mouse model and human preeclamptic placentas2018

    • Author(s)
      AKITOSHI NAKASHIMA
    • Organizer
      International Federation of Placenta Associations. Tokyo, Japan 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Autophagy is a new therapeutic target of preeclampsia: Trophoblasts-specific Atg7 knockout-mediated poor placentation induced hypertension in dams2018

    • Author(s)
      AKITOSHI NAKASHIMA
    • Organizer
      2018 Congress of the international society of Hypertension of pregnancy, Amsterdam, Netherland
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Autophagy Inhibition leads to Transthyretin Overload and Aggregation in Human Trophoblasts and Hepatocytes: Novel Implications for Preeclampsia2017

    • Author(s)
      Akitoshi Nakashima, Shi-Bin Cheng, Tae Kusabiraki, Aiko Aoki, Tomoko Shima, Osamu Yoshino, Surendra Sharma, Shigeru Saito.
    • Organizer
      37th American society of reproductive immunology meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Impaired autophagy and transthyretin protein aggregation in preeclampsia2017

    • Author(s)
      中島彰俊、草開妙、青木藍子、鮫島梓、島友子、吉野修、斎藤滋
    • Organizer
      第69回日本産科婦人科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] オートファジー不全によるトランスサイレチン蓄積が胎盤機能不全に関与する2017

    • Author(s)
      中島彰俊 草開妙 青木藍子 牛島明美 鮫島梓 島友子 吉野修 斎藤滋
    • Organizer
      第22回日本プロテアーゼ学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 早発妊娠高血圧症候群胎盤におけるオートファジー不全とトランスサイレチン蓄積の関与2017

    • Author(s)
      中島彰俊,草開妙,青木藍子,牛島明美,鮫島梓,島友子,吉野修,Surendra Sharma,斎藤滋
    • Organizer
      第25回日本胎盤学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 妊娠高血圧腎症胎盤におけるオートファジー不全とトランスサイレチン蓄積の関与2017

    • Author(s)
      中島彰俊,草開妙,青木藍子,牛島明美,鮫島梓,島友子,吉野修,Surendra Sharma,斎藤滋
    • Organizer
      第32回日本生殖免疫学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Preeclampsia serum disrupts the autophagy/lysosome pathway cooperated with endoplasmic reticulum (ER) stress2016

    • Author(s)
      Akitoshi Nakashima
    • Organizer
      10th INTERNATIONAL WORKSHOP in REUNION ISLAND
    • Place of Presentation
      Reunion Island, France
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 妊娠高血圧腎症患者血清は小胞体ストレスと共に絨毛細胞のオートファジーを破綻させる2016

    • Author(s)
      中島彰俊
    • Organizer
      第24回日本胎盤学会学術集会
    • Place of Presentation
      和歌山県和歌山市
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Preeclampsia serum disrupts the autophagy/lysosome pathway via inhibiting nuclear translocation of transcription factor EB2016

    • Author(s)
      Akitoshi Nakashima, Shi-Bin Cheng, Tomoko Shima, Surendra Sharma, Shigeru Saito.
    • Organizer
      American society fo reproductive immunology
    • Place of Presentation
      Baltimore, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 胎盤オートファジー抑制は妊娠高血圧症候群発症リスクである2016

    • Author(s)
      中島彰俊
    • Organizer
      第37回妊娠高血圧学会学術集会
    • Place of Presentation
      埼玉県大宮市
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 妊娠高血圧腎症発症機序の解明に向けてーlysosome/ Autophagy経路から観た新たな概念2016

    • Author(s)
      中島彰俊
    • Organizer
      第52回周産期新生児学会
    • Place of Presentation
      富山県富山市
    • Year and Date
      2016-07-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Preeclampsia (PE) serum disrupts the autophagy/lysosome pathway cooperated with endoplasmic reticulum (ER) stress.2016

    • Author(s)
      Akitoshi Nakashima, Tomoko Shima, Aiko Aoki, Kumiko Inada, Satoshi Yoneda, Arihiro Shiozaki, Osamu Yoshino, Surendra Sharma, Shigeru Saito
    • Organizer
      第68回日本産科婦人科学会
    • Place of Presentation
      東京
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Book] Preeclampsia Basic, Genomic, and Clinical2018

    • Author(s)
      Akitoshi Nakashima
    • Total Pages
      290
    • Publisher
      Springer
    • ISBN
      9789811058905
    • Related Report
      2018 Annual Research Report
  • [Book] Preeclampsia Basic, Genomic, and Clinical2018

    • Author(s)
      Akitoshi Nakashima, Shigeru Saito et al
    • Total Pages
      290
    • Publisher
      Springer
    • ISBN
      9789811058905
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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