Aquaporin membrane channels in the hepatobiliary tract: a model of complexity and clinical implications in health and disease

Abstract Aquaporins (AQPs) are transmembrane channel proteins that allow water and certain small solutes to pass through. In the liver, bile ducts, and gallbladder, AQPs are crucial in the pathways of hepatobiliary secretion and reabsorption. AQP8 and AQP9 are essential for facilitating the osmotic movement of water in hepatic bile, which is 95% water. In the biliary tract, AQP1 and AQP4 are involved in the rearrangement of bile composition by mechanisms of reabsorption/secretion of water. In the gallbladder, AQP1 and AQP8 are also involved in trans-epithelial bidirectional water flow with the ultimate goal of bile concentration. Pathophysiologically, AQPs have been indicated as players in several hepatobiliary disorders, including cholestatic diseases and cholesterol cholelithiasis. Research is ongoing to fully understand AQP function and how its expression is regulated, with scientists discovering powerful and specific compounds that can either boost or block these membrane channels, potentially leading to significant pharmaceutical advancements. This review summarizes the contribution of AQPs in physiological and pathophysiological stages related to hepatobiliary function.