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International Journal of Hepatology
Volume 2012 (2012), Article ID 452143, 9 pages
Review Article

Novel Approach to Bile Duct Damage in Primary Biliary Cirrhosis: Participation of Cellular Senescence and Autophagy

Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan

Received 30 March 2011; Accepted 20 April 2011

Academic Editor: Yoshiyuki Ueno

Copyright © 2012 Motoko Sasaki and Yasuni Nakanuma. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Primary biliary cirrhosis (PBC) is characterized by antimitochondrial autoantibodies (AMAs) in patients' sera and histologically by chronic nonsuppurative destructive cholangitis in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. The autoimmune-mediated pathogenesis of bile duct lesions, including the significance of AMAs, triggers of the autoimmune process, and so on remain unclear. We have reported that cellular senescence in biliary epithelial cells (BECs) may be involved in bile duct lesions and that autophagy may precede the process of biliary epithelial senescence in PBC. Interestingly, BECs in damaged bile ducts show characteristicsof cellular senescence and autophagy in PBC. A suspected causative factor of biliary epithelial senescence is oxidative stress. Furthermore, senescent BECs may modulate the microenvironment around bile ducts by expressing various chemokines and cytokines called senescence-associated secretory phenotypes and contribute to the pathogenesis in PBC.