Division of Gastroenterology and Hepatology and the Mayo Clinic Center for Cell Signaling in Gastroenterology, Mayo Clinic, Rochester, MN, USA.
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN, 55905, USA.
Semin Immunopathol. 2022 Jul;44(4):527-544. doi: 10.1007/s00281-022-00909-9. Epub 2022 Feb 17.
The cholangiopathies are a group of liver diseases that affect cholangiocytes, the epithelial cells that line the bile ducts. Biliary atresia (BA), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are three cholangiopathies with significant immune-mediated pathogenesis where chronic inflammation and fibrosis lead to obliteration of bile ducts and eventual liver cirrhosis. Cellular senescence is a state of cell cycle arrest in which cells become resistant to apoptosis and profusely secrete a bioactive secretome. Recent evidence indicates that cholangiocyte senescence contributes to the pathogenesis of BA, PBC, and PSC. This review explores the role of cholangiocyte senescence in BA, PBC, and PSC, ascertains how cholangiocyte senescence may promote a senescence-associated immunopathology in these cholangiopathies, and provides the rationale for therapeutically targeting senescence as a treatment option for BA, PBC, and PSC.
胆管疾病是一组影响胆管细胞的肝脏疾病，胆管细胞是排列在胆管内的上皮细胞。胆道闭锁（BA）、原发性胆汁性胆管炎（PBC）和原发性硬化性胆管炎（PSC）是三种具有显著免疫介导发病机制的胆管疾病，其中慢性炎症和纤维化导致胆管闭塞，最终导致肝硬化。细胞衰老是细胞周期停滞的一种状态，在此状态下，细胞对细胞凋亡产生抗性，并大量分泌生物活性分泌组。最近的证据表明，胆管细胞衰老有助于 BA、PBC 和 PSC 的发病机制。本综述探讨了胆管细胞衰老在 BA、PBC 和 PSC 中的作用，确定了胆管细胞衰老如何促进这些胆管疾病中的衰老相关免疫病理学，并为针对衰老作为 BA、PBC 和 PSC 的治疗选择进行治疗提供了依据。
