2023 Fiscal Year Final Research Report

Etiology and pathogenesis of biliary atresia elucidated by cell death patterns

Research Project

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Project/Area Number	21K08637
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Tohoku University
Principal Investigator	Hideyuki Sasaki 東北大学, 医学系研究科, 大学院非常勤講師 (40438461)
Co-Investigator(Kenkyū-buntansha)	工藤博典東北大学, 医学系研究科, 助教 (00723032) 大久保龍二東北大学, 大学病院, 助教 (00791865) 橋本昌俊東北大学, 医学系研究科, 大学院非常勤講師 (20897954)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	胆道閉鎖症 / 予後 / necroptosis
Outline of Final Research Achievements	We examined the association between necroptosis-related factors and clinical factors in a total of 103 cases, including 59 BA liver biopsies at the time of initial surgery, 14 liver explanted for liver transplantation after BA surgery, and 30 liver biopsies at the time of surgery for congenital biliary dilatation (CBD). The expression of TLR3, RIP1, and MLKL was significantly higher in the BA group than in the CBD group. Necroptosis was observed in intrahepatic bile duct epithelial cells in both BA and CBD but not in intrahepatic bile duct epithelial cells in the normal liver of neonates and infants. These results suggest that necroptosis is involved in the pathogenesis of BA. In a clinical study, γGTP showed a negative correlation with D-Bil in the early postoperative period and tended to increase during the period of increased bile excretion.
Free Research Field	小児外科学
Academic Significance and Societal Importance of the Research Achievements	未だ病因が未解明である胆道閉鎖症の病因・病態におけるネクロプトーシスの関与について検討を行ったことは意義がある。また今回の研究は単にネクロプトーシス関連分子の発現について検討したのみではなく、その臨床経過との比較を行って、一定の知見を得ることができた、という点についても学術的な意義があると考えられる。胆道閉鎖症は小児において肝移植をようする疾患の代表的な疾患であることより、このような研究を進めることは社会的にも意義深いものである。