Cholangiocytes, the epithelial cells that line the intrahepatic biliary tree, are the target of cholangiopathies, a wide array of chronic disorders that are characterized by the progressive vanishing of bile ducts, leading to ductopenia and
liver failure. The loss of bile ducts is a consequence of cholangiocyte death by apoptosis and impaired proliferative response of these cells to injury. The factors that regulate cholangiocyte proliferation and survival are poorly understood. In this regard, a major role is played by the interaction between
bile acids and the autonomic nervous system. It has been shown that
adrenergic and
cholinergic denervation of the liver results in the induction of cell death and impaired proliferative responses of the biliary epithelium to
cholestasis. In addition,
bile acids have been shown to enter cholangiocytes through the apical, Na(+)-dependent
bile acid transporter, ASBT, which has a marked impact on cholangiocyte pathobiology. Recent evidence shows that
bile acids and autonomic innervation interact in modulating cholangiocyte response to liver injury. In this review, we describe the recent advances in understanding the molecular mechanisms by which such events occur.