Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss

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.

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Erratum: Autophagy mediates the process of cellular senescence characterizing bile duct damages in primary biliary cirrhosis

Laboratory Investigation ◽

10.1038/labinvest.2010.195 ◽

2011 ◽

Vol 91 (6) ◽

pp. 968-968

Author(s):

Motoko Sasaki ◽

Masami Miyakoshi ◽

Yasunori Sato ◽

Yasuni Nakanuma

Keyword(s):

Bile Duct ◽

Primary Biliary Cirrhosis ◽

Cellular Senescence ◽

Biliary Cirrhosis

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Are bile duct lesions of primary biliary cirrhosis distinguishable from those of autoimmune hepatitis and chronic viral hepatitis? Interobserver histological agreement on trimmed bile ducts

Journal of Gastroenterology ◽

10.1007/s00535-004-1514-7 ◽

2005 ◽

Vol 40 (2) ◽

pp. 164-170 ◽

Cited By ~ 17

Author(s):

Yoh Zen ◽

Kenichi Harada ◽

Motoko Sasaki ◽

Koichi Tsuneyama ◽

Kazuhiro Matsui ◽

...

Keyword(s):

Bile Duct ◽

Primary Biliary Cirrhosis ◽

Autoimmune Hepatitis ◽

Viral Hepatitis ◽

Bile Ducts ◽

Chronic Viral Hepatitis ◽

Biliary Cirrhosis ◽

Bile Duct Lesions

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Biliary Epithelial Apoptosis, Autophagy, and Senescence in Primary Biliary Cirrhosis

Hepatitis Research and Treatment ◽

10.1155/2010/205128 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Motoko Sasaki ◽

Yasuni Nakanuma

Keyword(s):

Bile Duct ◽

Primary Biliary Cirrhosis ◽

Bile Ducts ◽

Experimental Studies ◽

Cholestatic Liver Disease ◽

Biliary Cirrhosis ◽

High Prevalence ◽

Small Bile Duct ◽

Bile Duct Lesions ◽

Autoimmune Pathogenesis

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized serologically by the high prevalence of anti-mitochondrial autoantibodies (AMAs) and histologically by the cholangitis of small bile ducts, eventually followed by extensive loss of the small bile duct. An autoimmune pathogenesis is suggested by clinical and experimental studies, but there remain issues regarding the etiology, the significance of AMAs in the pathogenesis of bile duct lesions, and so on. The unique properties of apoptosis in biliary epithelial cells (BECs), in which there is exposure of autoantigen to the effectors of the immune system, are proposed to be a cause of bile duct lesions in PBC. Recent progress disclosed that cellular senescence and autophagy are involved in bile duct lesions in PBC. Senescent BECs may modulate the periductal microenvironment by expressing senescence-associated secretory phenotypes, including various chemokines, and contribute to the pathogenesis of bile duct lesions in PBC.

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