Establishing the basis for new molecular-targeted therapies based on the signal transduction system by estrogen-related receptors for endometriosis
Project/Area Number |
18K09295
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Kitawaki Jo 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00204925)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 子宮内膜症 / エストロゲン関連受容体 / 分子標的治療 / イソフラボン |
Outline of Final Research Achievements |
Endometriosis grows and regresses in an estrogen-dependent manner. However, the classical estrogen receptor (ER)α-mediated signaling pathway is less dominant. The major pathway is that mediated via PGC-1α, a representative coactivator of estrogen-related receptor (ERR)α. In this study, we demonstrated that HX531, an antagonist of RXRα (one of the coactivators of PGC-1α), suppresses cell proliferation of endometriosis by inhibiting PGC-1α and suppressing the elevation of ERβ, IL-6 and IL-8, inflammatory cytokines, and survivin, an anti-apoptotic gene. Our findings suggest that the PGC-1α-mediated system is promising for establishing new therapeutic strategies.
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Academic Significance and Societal Importance of the Research Achievements |
従来、エストロゲン依存性増殖機構は古典的なERαを介するシグナル伝達経路によってのみ説明されてきたが、本研究では子宮内膜症においてPGC-1αを中心とした新たなエストロゲン依存性増殖機構を示した。 さらにこの系を阻害することによって子宮内膜症の細胞増殖が抑制されることを示した。現在まで子宮内膜症を完治させる治療法はなく、疼痛を緩和させるための内分泌療法が存在するのみであった。本研究成果は新たな治療戦略確立に有望であることが示された。
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Report
(4 results)
Research Products
(10 results)
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[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.
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Journal Title
Hum Reprod
Volume: 34
Issue: 6
Pages: 1019-1029
DOI
Related Report
Peer Reviewed
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[Journal Article] Daidzein-rich isoflavone aglycones inhibit cell growth and inflammation in endometriosis2018
Author(s)
Takaoka O, Mori T, Ito F, Okimura H, Kataoka H, Tanaka Y, Koshiba A, Kusuki I, Shigehiro S, Amami T, Kitawaki J
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Journal Title
J Steroid Biochem Mol Biol
Volume: 181
Pages: 125-132
DOI
Related Report
Peer Reviewed
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