Establishment of the molecular basis for the treatment of endometriosis based on the crosstalk between hepcidin and PGC1a

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16775
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• 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), 学内講師 (90849027)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ヘプシジン / 酸化ストレス / 子宮内膜症

Outline of Final Research Achievements

It was revealed that a high concentration of hepcidin is present in the menstrual blood of patients with endometriosis. Hepcidin causes a decrease in the membrane distribution concentration of ferroportin, the only transporter that expels iron from cells to the extracellular space, promoting intracellular iron concentration. Furthermore, excessive intracellular iron concentration leads to a relative decrease in NAD levels due to the promotion of ROS production, causing inflammatory changes not only in normal endometrial stromal cells but also in the stromal cells of endometriotic lesions. This suggests a deep involvement in the onset and progression of endometriosis. It was also found that bacterial endotoxin LPS plays an important role in the onset and pathogenesis, which can be suppressed by the administration of antioxidants.

Free Research Field

産婦人科、子宮内膜症

Academic Significance and Societal Importance of the Research Achievements

子宮内膜症の治療は専ら外科的治療とホルモン治療が行われてきたが、妊孕性の温存や副作用の回避のために新たな治療戦略の確立が望まれている。われわれは鉄代謝と酸化ストレスの観点から子宮内膜症の発症と病態進展に新たな知見を見出した。特に子宮内膜症を引き起こす細胞内に過剰の鉄が貯留することにより、細胞内の酸化ストレスが上昇、その細胞に炎症性変化を引き起こすことが明らかとなった。これらの分子学的機構については新たな治療ターゲットとして有用であると考えられ、さらなる研究を継続している。