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Elucidation of the PGC-1 alpha-mediated pathway of endometriosis and establishment of molecular targeted therapy

Research Project

Project/Area Number 19K24048
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0906:Surgery related to the biological and sensory functions and related fields
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Kataoka Hisashi  京都府立医科大学, 医学(系)研究科(研究院), 助教 (90849027)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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)
KeywordsPGC-1α / 低栄養 / 代謝 / 低酸素 / 子宮内膜症
Outline of Research at the Start

子宮内膜症の発症・進展機序はいまだ不明な点が多い。我々はこれまでに転写共役因子であるPGC-1αが子宮内膜症における細胞の増殖やエストロゲンの異常産生、局所の炎症惹起、抗アポトーシスの獲得など様々な病態形成に重要な役割を果たすことを明らかにしてきた。さらに病巣局所で異常産生されているTNF-αがさらにPGC-1αを誘導することを明らかにし、内分泌-炎症のクロストークの存在について示した。
本研究ではPGC-1αが相互作用を示すとされる核内受容体の同定とその複合体が及ぼすシグナル伝達経路を明らかにすることで、内分泌・炎症の両側面から病巣進展を制御しうる新たな治療戦略の分子基盤を確立させる。

Outline of Final Research Achievements

We have focused on the role of PGC-1α in the pathophysiology and progression of endometriosis. It was shown that RXR receptors, which are coactivators with PPAR receptors and other receptors, may act as homodimers and monomers in endometriosis. We also showed that PGC-1α may play a role in the pathophysiology of endometriosis by enhancing its function in local hypoxia and undernutrition, affecting glucogenesis and energy metabolism. In mice, we found that HX531, which suppresses RXR function, reduced the number and weight of endometriotic tissues. These results suggest that PGC-1α plays a central role in the pathophisiology of endometriosis and that HX531 may be useful as a novel therapeutic agent.

Academic Significance and Societal Importance of the Research Achievements

子宮内膜症は生殖年齢女性の約6-10%が罹患し、骨盤痛や不妊の原因となり生活のQOLを著しく低下させる。その病因は不明な点が多く、また従来の治療では再発のリスクや妊娠希望女性には使いづらいなど、新しい治療法の開発が望まれている。われわれが見出したPGC-1αは子宮内膜症の病態形成に中心的な役割を果たす因子であり、その詳細な検討から子宮内膜症の発症機序や増悪のメカニズムの解明に期待できる。またPGC-1αが共役するRXRの阻害剤を用いることで子宮内膜症の治療につながる可能性を見出した。これらは今までとは違う側面からの新規治療法であり、子宮内膜症の克服への一助となると考えられる。

Report

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

    (12 results)

All 2021 2020 2019

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (2 results)

  • [Journal Article] Interleukin‐9 produced by helper T cells stimulates interleukin‐8 expression in endometriosis2020

    • Author(s)
      Tarumi Yosuke、Mori Taisuke、Okimura Hiroyuki、Maeda Eiko、Tanaka Yukiko、Kataoka Hisashi、Ito Fumitake、Koshiba Akemi、Kusuki Izumi、Kitawaki Jo
    • Journal Title

      American Journal of Reproductive Immunology

      Volume: - Issue: 3

    • DOI

      10.1111/aji.13380

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Atherosclerosis-related biomarkers in women with endometriosis: The effects of dienogest and oral contraceptive therapy2020

    • Author(s)
      Maeda Eiko、Koshiba Akemi、Mori Taisuke、Ito Fumitake、Kataoka Hisashi、Okimura Hiroyuki、Sugahara Takuya、Tarumi Yosuke、Kusuki Izumi、Khan Khaleque N.、Kitawaki Jo
    • Journal Title

      European Journal of Obstetrics & Gynecology and Reproductive Biology: X

      Volume: 7 Pages: 100108-100108

    • DOI

      10.1016/j.eurox.2020.100108

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peroxisome proliferator-activated receptor-γ coactivator 1α-mediated pathway as a possible therapeutic target in endometriosis.2019

    • Author(s)
      Kataoka H, Mori T, Okimura H, Matsushima H, Ito F, Koshiba A, Tanaka Y, Akiyama K, Maeda E, Sugahara T, Tarumi Y, Kusuki I, Khan KN, Kitawaki J.
    • Journal Title

      Hum Reprod

      Volume: 34 Issue: 6 Pages: 1019-1029

    • DOI

      10.1093/humrep/dez067

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Local estrogen formation and its regulation in endometriosis2019

    • Author(s)
      Mori Taisuke、Ito Fumitake、Koshiba Akemi、Kataoka Hisashi、Takaoka Osamu、Okimura Hiroyuki、Khan Khaleque N.、Kitawaki Jo
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 18 Issue: 4 Pages: 305-311

    • DOI

      10.1002/rmb2.12285

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PGC-1αは子宮内膜症病態形成に関与する2019

    • Author(s)
      片岡 恒
    • Journal Title

      日本生殖内分泌学会雑誌

      Volume: 24 Pages: 9-11

    • Related Report
      2019 Research-status Report
  • [Journal Article] Antitumor effect of XCT790, an ERRα inverse agonist, on ERα-negative endometrial cancer cells.2019

    • Author(s)
      Kokabu T, Mori T, Matsushima H, Yoriki K, Kataoka H, Tarumi Y, Kitawaki J.
    • Journal Title

      Celler Oncology

      Volume: 42(2) Issue: 2 Pages: 223-235

    • DOI

      10.1007/s13402-019-00423-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Equilin in conjugated equine estrogen increases monocyte-endothelial adhesion via NF-κB signaling2019

    • Author(s)
      Ito F, Mori T, Tarumi Y, Okimura H, Kataoka H, Tanaka Y, Koshiba A, Kitawaki J
    • Journal Title

      PLoS One

      Volume: 14 Issue: 1 Pages: 1-14

    • DOI

      10.1371/journal.pone.0211462

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腸型腺癌への悪性転化をきたした卵巣成熟奇形腫の1例2020

    • Author(s)
      片岡 恒、垂水 洋輔、古株 哲也、寄木 香織、森 泰輔、北脇 城
    • Organizer
      第62回日本婦人科腫瘍学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Hepcidin as a key regulator of iron in the pathogenesis of endometriosis and a new biomarker2019

    • Author(s)
      Hisashi Kataoka, Taisuke Mori, Fumitake, Ito, Akemi, Koshiba, Hiroyuki Okimura, Eiko Maeda, Yosuke Tarumi, Takuya Sugahara, Koki Shimura, Izumi Kusuki, and Jo Kitawaki
    • Organizer
      The 71th Annual Congress of the Japan Society of Obstetrics and Gynecology
    • Related Report
      2019 Research-status Report
  • [Presentation] Hepcidin promotes iron accumulation and triggers inflammatory features of normal endometrium2019

    • Author(s)
      Hisashi Kataoka, Taisuke Mori, Izumi Kusuki Khaleque N Khan , Jo Kitawaki
    • Organizer
      Asian Conference of Endometriosis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Book] 子宮内膜症・子宮腺筋症ー診断アトラス&新たな治療戦略2021

    • Author(s)
      大須賀穣、甲賀かをり
    • Total Pages
      304
    • Publisher
      中山書店
    • ISBN
      9784521749105
    • Related Report
      2020 Annual Research Report
  • [Book] 産科と婦人科2020

    • Author(s)
      片岡 恒
    • Total Pages
      130
    • Publisher
      (株)診断と治療社
    • Related Report
      2019 Research-status Report

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Published: 2019-09-03   Modified: 2022-01-27  

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