Elucidation of the mechanisms of vulnerability of neonatal kidney

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05889
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Yoshioka Wataru 東京慈恵会医科大学, 医学部, 講師 (80425496)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 水腎症 / 多尿 / 尿濃縮障害 / プロスタグランジン

Outline of Final Research Achievements

Arylhydrocarbon receptor (AhR) is a ligand-dependent transcription factor that is responsible for dioxin toxicity. The mechanisms linking AhR and dioxin toxicity has been largely unknown. In this study, we found that a phospholipase cPLA2a has a potential to link AhR and dioxin toxicity. In addition, we found that an increase and dilution of urine is a direct mechanism of hydronephrosis, one of developmental-stage specific dioxin toxicity, and that the mechanism is not induced in adults. These findings offered important insights into the problem of developmental-stage specific toxicity of dioxins as well as mechanisms of vulnerability of neonatal kidney.

Free Research Field

毒性学

Academic Significance and Societal Importance of the Research Achievements

化学物質の生体影響について、発達段階のある時期には悪影響が生じて別の時期には影響が生じないことがある。このように発達段階特異性があることは化学物質の影響評価を困難にする問題であるが、その原因はよく分かっていない。本研究では、芳香族炭化水素類等がマウス新生子に引き起こす水腎症をモデルとして、発症機序をまず解明し、次いで水腎症が生じない時期にこの機序が作動しないことを明らかにした。機序を解明することで発達段階特異性が生じる原因が明らかにできることが示された。