The Role of Extracellular Vesicles in Mediating Signaling in Biliary Epithelial Cell Activation and Cholangiopathies

Abstract

Cholangiopathies, a diverse group of diseases affecting the biliary tract, are characterized by ac-tivation of cholangiocytes, fibrosis, and inflammation. Recent research hasidentified extracellular vesicles (EVs) as crucial mediators of communication within the hepatobiliary system. This review aims to explore the impact of EVs on cholangiocyte behavior and their role in disease develop-ment. EVs originating from cholangiocytes, hepatocytes, and immune cells carry a variety of mol-ecules, including non-coding RNAs, proteins, and lipids, which influence immune responses, fi-brosis, and epithelial repair. Specifically, EVs released by activated or senescent cholangiocytes can worsen inflammation and fibrosis by delivering molecules such as lncRNA H19, miR-21, and damage-associated molecular patterns(DAMPs) to hepatic stellate and immune cells. Additionally, the polarity and content of EVs are influenced by specific subcellular domains of cholangiocytes, indicating distinct signaling functions. In conditions such as primary sclerosing cholangitis (PSC), cholangiocarcinoma (CCA), and biliary atresia, EVs play a role in disease progression and offer potential as non-invasive biomarkers and therapeutic targets. This review underscores the im-portance of in-depth profiling and validation of EVs to fully utilize their diagnostic and therapeu-tic capabilities. Overall, EV-mediated signaling is a critical mechanism in cholangiopathies, providing a new avenue for understanding disease progression and developing precision medi-cine approaches.