| Project/Area Number |
18K09259
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Mogami Haruta 京都大学, 医学研究科, 助教 (40378766)
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| Co-Investigator(Kenkyū-buntansha) |
近藤 英治 京都大学, 医学研究科, 准教授 (10544950)
万代 昌紀 京都大学, 医学研究科, 教授 (80283597)
千草 義継 京都大学, 医学研究科, 助教 (80779158)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 前期破水 / 羊膜 / マクロファージ / 創傷治癒・再生 / 早産 / 治癒・再生 / 上皮間葉転換 / グルココルチコイド / 創傷治癒 / 自然免疫 |
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| Outline of Final Research Achievements |
Preterm premature rupture of membranes (pPROM) is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. In this study, we investigated the mechanisms of amnion healing using conditional macrophage-depleted mice. At the rupture site of both human and mouse amnion, macrophages migrated to and reside in the ruptured site, where the epithelial-mesenchymal transition (EMT) was observed. In vivo, the wound healing of amnion was significantly compromised in the conditionally macrophage-depleted mice, and the EMT was absent. In vitro, the migration of amnion was mediated by the EMT through the TGF-β-Smad signal. In the cases of human pPROM, macrophages were also migrated to the ruptured site of amnion with the evidence of EMT. These findings suggest the importance of fetal macrophages in the healing of amnion through induction of the EMT.
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| Academic Significance and Societal Importance of the Research Achievements |
早産は、児が未熟な状態、かつ低体重で出生するため、周産期死亡の一番の原因であり、さらに児に後遺症を残すことがあり、周産期医学・社会的に大きな問題である。満期に至る前に破水する前期破水は早産の主要な病因であるが、その予防・治療法は確立されていない。本研究は、自然免疫のマクロファージの助けにより、破水した羊膜上皮細胞が間葉細胞に転換しながら羊膜が治癒していくことが示され、羊膜の治癒・再生機構の一端を解明できた。この研究成果は前期破水の予防・治療への礎となり、将来、早産を減らすための第一歩となると考えられる。
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