Central role for cholangiocyte pathobiology in cholestatic liver diseases

胆管上皮细胞 肝病学 医学 旁分泌信号 纤维化 趋化因子 串扰 炎症 免疫学 癌症研究 生物 病理 内科学 受体 物理 光学
作者
Nidhi Jalan‐Sakrikar,Maria Eugenia Guicciardi,Steven P. O’Hara,Adiba Azad,Nicholas F. LaRusso,Gregory J. Gores,Robert C. Huebert
出处
期刊:Hepatology [Wiley]
卷期号:82 (4): 834-854 被引量:14
标识
DOI:10.1097/hep.0000000000001093
摘要

Cholangiopathies comprise a spectrum of chronic intrahepatic and extrahepatic biliary tract disorders culminating in progressive cholestatic liver injury, fibrosis, and often cirrhosis and its sequela. Treatment for these diseases is limited, and collectively, they are one of the therapeutic “black boxes” in clinical hepatology. The etiopathogenesis of the cholangiopathies likely includes disease-specific mediators but also common cellular and molecular events driving disease progression (eg, cholestatic fibrogenesis, inflammation, and duct damage). The common pathways involve cholangiocytes, the epithelial cells lining the intrahepatic and extrahepatic bile ducts, which are central to the pathogenesis of these disorders. Current information suggests that cholangiocytes function as a signaling “hub” in biliary tract-associated injury. Herein, we review the pivotal role of cholangiocytes in cholestatic fibrogenesis, focusing on the crosstalk between cholangiocytes and portal fibroblasts and HSCs. The proclivity of these cells to undergo a senescence-associated secretory phenotype, which is proinflammatory and profibrogenic, and the intrinsic intracellular activation pathways resulting in the secretion of cytokines and chemokines are reviewed. The crosstalk between cholangiocytes and cells of the innate (neutrophils and macrophages) and adaptive (T cells and B cells) immune systems is also examined in detail. The information will help consolidate information on this topic and guide further research and potential therapeutic strategies for these diseases.
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