| Project/Area Number |
15K20169
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
TSUZUKI Tomoko 関西医科大学, 医学部, 嘱託医員 (00465642)
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| Project Period (FY) |
2015-04-01 – 2020-03-31
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| Project Status |
Discontinued (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 異所性子宮内膜 / VEGF / HIF-1 / エキノマイシン / アポトーシス / 子宮内膜症細胞 / SDF-1 / 低酸素刺激 / 異所性子宮内膜症 |
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| Outline of Final Research Achievements |
Recent evidence points to a possible role for HIF-1 in the development of endometriosis. The objectives of this study were to investigate the critical role of HIF-1 in endometriosis and the effect of the HIF-1 inhibitor echinomycin on human ectopic endometriotic stromal cells (eESCs). Hypoxic stress induced expression of HIF-1a protein and VEGF production in eESCs, and VEGF production was significantly suppressed by treatment of echinomycin without causing cell toxicity. Synthetic progestins, including MPA and DNG, are used to treat endometriosis. In the present study, we were unable to demonstrate the inhibitory effects of MPA and DNG on VEGF production in eESCs. Therefore, echinomycin might be more useful than progestins as an inhibitor of VEGF production to regulate the angiogenesis of endometriosis. Moreover, echinomycin inhibited cell proliferation and induced apoptotic cell death of the eESCs, and significantly inhibited expression of the anti-apoptotic proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
子宮内膜症病変の進展に重要と思われる血管新生因子の発現とその調節機構の一部を解明することができた。またHIF-1阻害剤のEMはこれまでのホルモン製剤とは全く異なる機序で異所性子宮内膜細胞の増殖を抑制し、子宮内膜症の治療薬となる可能性を持っている。またEMは子宮内膜症への作用として血管新生因子の阻害のみならずアポトーシス効果も期待できる薬剤であることがわかった。本研究により子宮内膜症における血管新生の新たな制御機構を解明し、さらに血管新生因子やHIF-1をターゲットとした新規治療戦略として、実地診療への応用が期待される。
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