Regulation and deregulation of cholangiocyte proliferation

Abstract

HOLANGIOCYTES C are the epithelial cells which line the intrahepatic biliary tree, a network of interconnecting ducts of increasing diameter from the duct of Hering to the extrahepatic bile ducts (l-6). Cholangiocytes determine the final bile composition through a series of secretory and absorptive processes regulated by a number of hormones and neuropeptides (2-5). The intrahepatic bile ducts are the target of damage in a group of chronic cholestatic liver diseases recently classified as Vanishing Bile Duct Syndromes (4,7-9). These diseases are characterized by the progressive disappearance of intrahepatic bile ducts, which leads to a severe ductopenic condition in the terminal stages (79). The residual bile ducts tend to proliferate as a compensatory mechanism (8). Thus, the course of these diseases is characterized by a balance between damage (loss) of bile ducts and compensatory proliferation of the residual ducts. The terminal decompensated stages are characterized by the inefficacy of proliferation to balance for the loss of intrahepatic bile ducts. Therefore, a therapeutic strategy designed to support efficacious cholangiocyte proliferation could delay progression to ductopenia. This represents a challenge for the future. The aim of this review is to focus on current knowledge of the regulation and dysregulation of cholangiocyte proliferation.