Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari "Aldo Moro", 70121 Bari, Italy.
Department of Biosciences, Biotechnologies and Environment, University of Bari "Aldo Moro", 70125 Bari, Italy.
Int J Mol Sci. 2024 Nov 12;25(22):12133. doi: 10.3390/ijms252212133.
Aquaporins (AQPs) are transmembrane proteins permeable to water and a series of small solutes. AQPs play a key role in pathways of hepatobiliary secretion at the level of the liver, bile ducts, and gallbladder. AQP8 and -9 are pivotal in facilitating the osmotic water movement of hepatic bile, which is composed of 95% water. In the biliary tract, AQP1 and -4 are involved in the rearrangement of bile composition by mechanisms of reabsorption/secretion of water. In the gallbladder, AQP1 and -8 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 on AQP function and the modulation of AQP expression is in progress, with the identification of potent and homolog-specific compounds modulating the expression or inhibiting these membrane channels with promising pharmacological developments. This review summarizes the contribution of AQPs in physiological and pathophysiological stages related to hepatobiliary function.
水通道蛋白（AQP）是一类可通透水和一系列小分子溶质的跨膜蛋白。AQP 在肝脏、胆管和胆囊水平的肝胆分泌途径中发挥关键作用。AQP8 和 -9 对于促进由 95%水组成的肝胆汁的渗透水运动至关重要。在胆道中，AQP1 和 -4 通过水的重吸收/分泌机制参与胆汁成分的重排。在胆囊中，AQP1 和 -8 也参与跨上皮双向水流动，最终目的是使胆汁浓缩。在病理生理学上，AQP 已被确定为几种肝胆疾病的参与者，包括胆汁淤积性疾病和胆固醇胆石症。对 AQP 功能和 AQP 表达的调节的研究正在进行中，已经鉴定出具有潜在和同源特异性的化合物来调节这些膜通道的表达或抑制这些膜通道，具有有前景的药理学发展。本综述总结了 AQP 在与肝胆功能相关的生理和病理生理阶段的贡献。
