Dysregulation of Apoptosis in the Cholangiopathies and Cholangiocarcinoma

ABSTRACT

The importance of cholangiocytes, the epithelial cells lining bile ducts, in the biology andpathobiol-ogy of biliary epithelia is rapidly growing due to the advent of suitable experimental models and techniques to study these cells. However, the role of cholangiocytes as a major cellular target in a variety of severe hepatobiliary diseases or cholangiopathies remains unanswered. As the biology of cholangiocyte death evolves, apoptosis has emerged as a key player in the development of ductopenia in these cholangiopathies. Cholangiocytes are continuously exposed to a variety of genotoxic insults, such as chronic inflammation and hydrophobic bile acids. This chronic exposure may predispose cholangiocytes to oncogenic mutations and the further progression to malignancy (or cholangiocarcinoma [CC]), due, in part, to failure to activate apoptosis and delete cells with genetic damage.

KEY WORDS

cholangiocytes - bile duct epithelial cells - cholangiocarcinoma - cholangiopathies - ductopenia