Elucidation of molecular mechanisms targeting oxygen-induced vascular remodeling on ductus arteriosus closure

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08282
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kagawa Nutrition University (2023); Jikei University School of Medicine (2019-2022)
• Principal Investigator: Akaike Toru 女子栄養大学, 栄養学部, 教授 (20647101)
• Co-Investigator(Kenkyū-buntansha): 南沢 享 東京慈恵会医科大学, 医学部, 教授 (40257332)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 動脈管

Outline of Final Research Achievements

In this study, we performed DNA microarray on fetal rat ductus arteriosus and pulmonary arterial tissues to investigate genetic changes between before and after birth in order to clarify the molecular mechanism of oxygen-related ductus arteriosus closure after birth. We selected genes whose expression increased or decreased at 2 days after birth compared to embryonic day 21st. In the ductus arteriosus, the expression of Vegfa, Hmox1, Angptl4, Spp1, and Itga10 was especially increased, and the expression of Afp, Adgrg6, and Ankrd1 was especially decreased. These genes are involved in angiogenesis, cell proliferation/migration, and extracellular matrix production under hypoxic conditions, and we will continue to investigate their effects on ductus arteriosus closure.

Free Research Field

小児循環器学

Academic Significance and Societal Importance of the Research Achievements

生後に動脈管が閉鎖しない疾患である動脈管開存症の薬物的治療は、プロスタグランジンEを治療標的とする非ステロイド性抗炎症薬のみである。しかしながら、動脈管開存症を発症しやすい早期産児や低出生体重児では、薬物治療により壊死性腸炎や腎不全などの副作用を生じやすい。そのため、非ステロイド性抗炎症薬に替わる新たな治療薬の開発が望まれている、そこで、本研究成果を基にさらなる研究を行い、動脈管の閉鎖作用をもつ遺伝子を同定し、最終的に動脈管開存症の新たな治療薬を開発することが期待される。