Dysregulation of apoptosis in the cholangiopathies and cholangiocarcinoma.
The importance of cholangiocytes, the epithelial cells lining bile ducts, in the biology and pathobiology 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.
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Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
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D017209:Apoptosis / Q000502:physiology*; D001650:Bile Duct Neoplasms / Q000473:pathology*; D001652:Bile Ducts / Q000166:cytology; D001660:Biliary Tract Diseases / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000473:pathology*; D006801:Humans