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

Cholangiopathies, a diverse group of diseases affecting the biliary tract, are characterized by the activation of cholangiocytes, fibrosis, and inflammation. Recent research has identified 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 development. EVs originating from cholangiocytes, hepatocytes, and immune cells carry a variety of molecules, including non-coding RNAs, proteins, and lipids, which influence immune responses, fibrosis, 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 importance of in-depth profiling and validation of EVs to fully utilize their diagnostic and therapeutic capabilities. Overall, EV-mediated signaling is a critical mechanism in cholangiopathies, providing a new avenue for understanding disease progression and developing precision medicine approaches.