Analysis of molecular mechanisms in the development of pediatric cholestatic liver disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 20KK0172
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Hayashi Hisamitsu 東京大学, 大学院薬学系研究科(薬学部), 准教授 (10451858)
• Co-Investigator(Kenkyū-buntansha): 戸川 貴夫 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (10792814) ; 今川 和生 筑波大学, 医学医療系, 講師 (40708509) ; 水野 忠快 東京大学, 大学院薬学系研究科(薬学部), 助教 (90736050)
• Project Period (FY): 2020-10-27 – 2024-03-31
• Keywords: 小児肝疾患 / 肝内胆汁うっ滞 / 胆汁酸

Outline of Final Research Achievements

Childhood-onset intrahepatic cholestasis includes many inherited rare liver diseases, but the definitive diagnosis rate is less than 30% because the causative gene is unknown in many cases.
Treatment for this disease has not yet been established because the molecular mechanism underlying cholestasis development has not been elucidated. This study aimed to identify a novel causative gene for this disease and elucidate the molecular mechanism of cholestasis caused by the gene abnormality.
We analyzed clinical information and biological samples from patients with intrahepatic cholestasis to search for candidate causative genes. We then experimentally evaluated the candidate genes and verified their involvement in the development of intrahepatic cholestasis. As a result, we identified the genes responsible for the development of intrahepatic cholestasis and the mechanism by which abnormality of these genes causes it.

Free Research Field

分子病態学、肝臓学

Academic Significance and Societal Importance of the Research Achievements

小児期発症の肝内胆汁うっ滞症には、多数の遺伝性稀少肝疾患が包含されるが、未同定変異が多数存在するため、確定診断率は30%に満たない。また病態分子基盤が不明なため治療法が未確立である。本研究では、肝内胆汁うっ滞を呈する患児の臨床情報、生体試料の活用、及び実験科学的な検証により、本疾患の新規原因遺伝子の同定、及び当該遺伝子の破綻が病態発症を来す分子基盤について示唆を得るに至った。