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2021 Fiscal Year Final Research Report

Development of a novel therapeutic approach for fibropolycystic liver disease focusing on cellular senescence of cholangiocytes

Research Project

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Project/Area Number 19K07458
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionKanazawa University

Principal Investigator

Sato Yasunori  金沢大学, 医学系, 准教授 (30324073)

Project Period (FY) 2019-04-01 – 2022-03-31
Keywords人体病理学 / 肝臓 / 胆管細胞 / 肝線維嚢胞性疾患
Outline of Final Research Achievements

This study revealed that activation of the Notch-Hes1 signaling pathway was critically involved in biliary cystogenesis of Caroli disease with congenital hepatic fibrosis (CHF) as well as the polycystic kidney (PCK) rat, an animal model of Caroli disease with CHF. In vitro experiments using PCK cholangiocytes showed that administration of Notch inhibitor (FLI-06) significantly inhibited cell proliferative activity. The inhibition was accompanied by the induction of apoptosis, but not cellular senescence. These results indicate that inhibition of the Notch signaling represents a potential target of therapy for Caroli disease with congenital hepatic fibrosis.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

Caroli病は肝内胆管の進行性の拡張を来す先天性疾患で,多くの症例は先天性肝線維症を合併する。Caroli病 + 先天性肝線維症の患者予後を規定する臨床因子として,胆管拡張に起因する胆管炎と先天性肝線維症による門脈圧亢進症が重要であるが,現在の治療は対症療法が主体で重症例には肝移植が行われている。本研究は胆管細胞におけるNotchシグナル伝達系を阻害することで,Caroli病の胆管拡張を抑制しうることを示した。一連の研究成果は新たな治療法の開発に繋がる可能性を有している。

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Published: 2023-01-30  

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