2023 Fiscal Year Final Research Report
Elucidation of the molecular mechanism of ductus arteriosus closure
Project/Area Number |
21H02884
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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Research Institution | Jikei University School of Medicine |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
井上 天宏 東京慈恵会医科大学, 医学部, 講師 (00349557)
赤池 徹 東京慈恵会医科大学, 医学部, 准教授 (20647101)
暮地本 宙己 東京慈恵会医科大学, 医学部, 講師 (60632841)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | 動脈管 / 転写因子 / 内膜肥厚 / メタボローム / ミトコンドリア |
Outline of Final Research Achievements |
The purpose of this study was to elucidate the molecular mechanisms of functional and structural closure of ductus arteriosus and to develop new therapeutic strategies. To this end, we investigated the effects of polyphenols on ductal contraction and remodeling, the role of the transcription factor NR4A1 in ductal closure, and the mitochondrial functional characteristics of ducts before and after birth. We found that resveratrol significantly constricts ductus arteriosus and decreases the expression of Cox2 and EP4, that Nr4a1 expression is significantly increased by oxygenation and that Nr4a1 has the ability to promote hyaluronic acid production, and that mitochondrial respiration and glycolytic system activity may be decreased after birth in ductus arteriosus The study is a key step in the future development of drugs for ductus arteriosus wound healing. This study provides a basis for future arteriolar drug discovery.
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Free Research Field |
発達循環器学
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Academic Significance and Societal Importance of the Research Achievements |
動脈管閉鎖機転を知ることは、未熟児ならびに先天性心疾患患児をはじめ、小児医療上、極めて重要な研究課題である。本研究は、これまでに十分に検討が及んでいなかった観点から、動脈管の分化・成熟に関わる分子機序を検討し、動脈を選択的かつ効果的に閉鎖させる新たな治療法の確立にむけて展開ができると考えている。未熟児・新生児医療の現場からは、PGE2合成阻害剤やPGE2製剤に代わる新たな治療法の開発が強く望まれており、本研究の意義は臨床的にも極めて大きい。
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