Regulation of pharmacokinetics during pregnancy by placental exosomes

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21489
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Keio University
• Principal Investigator: Tomi Masatoshi 慶應義塾大学, 薬学部(芝共立), 教授 (30334717)
• Co-Investigator(Kenkyū-buntansha): 石川 源 日本医科大学, 医学部, 講師 (20287767) ; 野口 幸希 慶應義塾大学, 薬学部(芝共立), 助教 (10803661) ; 西村 友宏 慶應義塾大学, 薬学部(芝共立), 准教授 (40453518)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 胎盤

Outline of Final Research Achievements

Syncytin-2, a molecule specifically expressed in the placenta, has membrane fusion capacities and contributes to the barrier formation through syncytialization. In this study, it is indicated that the uptake of JEG-3 cell-derived exosome to human hepatic HepG2 cells was significantly enhanced when the expression of syncytin-2 in JEG-3 cells was induced. The placenta-specific miRNA is detected from HepG2 cells exposed to JEG-3 cell-derived exosomes, implying that exosomal syncytin-2 is capable to mediate cell-to-cell communication through the exosome. However, the expression of MFSD2A, a receptor of syncytin-2, is found not to be constitutively expressed in the mouse liver. Therefore, it is necessary to further confirm whether syncytin-2-expressing exosome is preferably binds to hepatic cells. We also found that MFSD2A involves in the supply of docosahexaenoic acid to the fetus.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

Syncytin-2は胎盤特異的に発現する分子であり、本研究では本分子を発現する胎盤細胞由来のエクソソームが細胞間の情報伝達の促進に貢献する可能性を示す結果を得ることができた。妊娠期における胎盤から母体への情報発信メカニズムを新たに提唱する先駆的結果である。ただし、受容体となるMFSD2Aの発現細胞は限られており、血液脳関門には発現していることが確認できた一方で、肝臓においては恒常的に発現していないことも明らかとなった。妊娠期における薬物代謝の変動に本メカニズムが関与している可能性については、慎重な評価が必要である。