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

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24048
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyoto 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
• Keywords: PGC-1α / 低栄養 / 代謝

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.

Free Research Field

子宮内膜症

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。