Elucidation of mechanisms of Flt1 gene expression in trophoblast cells by HIF-2 alpha under physiological and pathological conditions

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09675
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Jobu University
• Principal Investigator: SASAGAWA Tadashi 上武大学, 医学生理学研究所, 研究員 (30424675)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Flt1 / HIF-2α / HIF-1β / 妊娠高血圧症候群 / 栄養膜細胞 / 転写制御

Outline of Final Research Achievements

In this study, the expression mechanisms of the Flt1 gene mediated by HIF-2α in trophoblast cells under normoxic and hypoxic conditions were investigated. The results revealed the involvement of HIF-1β, the dimerization partner of HIF-2α, in both culture conditions. Furthermore, it was also suggested that the locations of candidate hypoxia response elements on the Flt1 gene to which HIF-2α binds may differ between the respective culture conditions.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

妊娠高血圧症候群(PE)の病態進行には、胎盤の栄養膜細胞より過剰分泌される抗血管新生因子sFlt1が中心的役割を果たしている。本研究により、栄養膜細胞が低酸素ストレスを受けるとHIF-2αとHIF-1βが協力してsFlt1分泌を増強させることが明らかとなった。現時点においてPEの治療薬は確立されておらず、本成果はHIF-2αとHIF-1βの複合体形成阻害がPEの新たな治療戦略となる可能性を示唆するものである。