Elucidation of a Novel Inflammatory Mechanism Mediated by Extracellular Vesicles in Primary Sclerosing Cholangitis Using Organoid Culture

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17010
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Yamagata University
• Principal Investigator: Katsumi Tomohiro 山形大学, 医学部, 助教 (70637355)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細胞外小胞

Outline of Final Research Achievements

To elucidate a novel mechanism by which extracellular vesicles (EVs) induce the bile duct damage characteristic of primary sclerosing cholangitis, we cultured bile duct epithelial cells and extracted EVs released from them. EVs proteins were differentially expressed on the luminal and basement membrane sides of bile duct epithelial cells, with specific expression of S100 protein. shRNA knockdown of EVs from the cells and stimulation of inflammatory cells resulted in increased expression of inflammatory cytokines (TNFα, IL-1β, and IL-6). These results suggest that EVs from bile duct epithelial cells are involved in the pathogenesis of cholangitis and other diseases.

Free Research Field

自己免疫性肝疾患

Academic Significance and Societal Importance of the Research Achievements

今回の検証では細胆管上皮細胞培養技術によりEVs抽出が可能となった。またそれらのEVs刺激により炎症性サイトカインが上昇することが判明した。これらはPSCの胆管周囲炎症の病態に関与するものと思われる。すなわち胆管障害による細胆管反応が胆管周囲の炎症を惹起するEVsを放出しすることが考えられる。PSCは根治療法として肝移植しかない状況であるが、この炎症誘導機序の解明により、新たな治療が展開され難治性疾患の予後を延長させることが期待できる。