A comprehensive analysis of aquaporin and secretory related gene expression in neonate and adult cholangiocytes

Canalicular bile is secreted by hepatocytes and then passes through the intrahepatic bile ducts, comprised of cholangiocytes, to reach the extrahepatic biliary system. In addition to providing a conduit for bile to drain from the liver, cholangiocytes play an active role in modifying bile composition. Bile formation is the result of a series of highly coordinated intricate membrane-transport interactions. Proper systematic regulation of solute and water transport is critical for both digestion and the health of the liver, yet our knowledge of cholangiocyte water and ion transporters and their relative expression patterns remains incomplete. In this report, we provide a comprehensive expression profile of the aquaporin (AQP) family and three receptors/channels known to regulate ion transport in the murine cholangiocyte. In murine intrahepatic cholangiocytes, we found mRNA expression for all twelve of the members of the AQP family of proteins and found temporal changes in the expression profile occurring with age. Using AQP4, an established marker within cholangiocyte physiology, we found that AQP2, AQP5 and AQP6 expression levels to be significantly different between the neonatal and adult time points. Furthermore, there were distinct temporal expression patterns, with that of AQP12 unique in that its expression level decreased with age, whilst the majority of AQPs followed an increasing expression level trend with age. Of the three receptors/channels regulating ion transport in the murine cholangiocyte, only the cystic fibrosis transmembrane conductance regulator was found to follow a consistent trend of decreasing expression coincident with age. We have further validated AQP3 and AQP8 protein localization in both hepatocytes and cholangiocytes. This study emphasizes the need to further appreciate and consider the differences in cholangiocyte biology when treating neonatal and adult hepatobiliary diseases.