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

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Motoko Sasaki ◽  
Yasuni Nakanuma
Keyword(s):  
Bile Duct ◽  
Primary Biliary Cirrhosis ◽  
Cellular Senescence ◽  
Bile Ducts ◽  
Causative Factor ◽  
Biliary Cirrhosis ◽  
Novel Approach ◽  
Bile Duct Damage ◽  
Chronic Nonsuppurative Destructive Cholangitis ◽  
Bile Duct Lesions

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.

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

2005 ◽  
Vol 205 (4) ◽  
pp. 451-459 ◽  
Author(s):  
Motoko Sasaki ◽  
Hiroko Ikeda ◽  
Hironori Haga ◽  
Toshiaki Manabe ◽  
Yasuni Nakanuma
Keyword(s):  
Bile Duct ◽  
Primary Biliary Cirrhosis ◽  
Cellular Senescence ◽  
Bile Ducts ◽  
Biliary Cirrhosis

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

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
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.

Pathology and Immunopathology of Primary Biliary Cirrhosis With Emphasis On Bile Duct Lesions: Recent Progress

1995 ◽  
Vol 15 (04) ◽  
pp. 313-328 ◽  
Author(s):  
Yasuni Nakanuma ◽  
Koichi Tsuneyama ◽  
M. Gershwin ◽  
Mitsue Yasoshima
Keyword(s):  
Bile Duct ◽  
Primary Biliary Cirrhosis ◽  
Recent Progress ◽  
Biliary Cirrhosis ◽  
Bile Duct Lesions

Immunopathology of Bile Duct Lesions of Primary Biliary Cirrhosis

2017 ◽  
pp. 73-84
Author(s):  
Hayato Baba ◽  
Ayumi Sugitani ◽  
Ryusei Takahashi ◽  
Kouki Kai ◽  
Yuki Moritoki ◽  
...  
Keyword(s):  
Bile Duct ◽  
Primary Biliary Cirrhosis ◽  
Biliary Cirrhosis ◽  
Bile Duct Lesions

Bile Acids and Deregulated Cholangiocyte Autophagy in Primary Biliary Cholangitis

2017 ◽  
Vol 35 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Motoko Sasaki ◽  
Yasuni Nakanuma
Keyword(s):  
Bile Duct ◽  
Er Stress ◽  
Bile Acids ◽  
Cellular Senescence ◽  
Primary Biliary Cholangitis ◽  
Biliary Cirrhosis ◽  
Chemical Chaperone ◽  
Abnormal Expression ◽  
Bile Duct Lesions ◽  
Mitochondrial Antigens

Background: Primary biliary cholangitis (PBC) is characterized by a high prevalence of serum anti-mitochondrial antibodies against the E2 subunit of the pyruvate dehydrogenase complex and bile duct lesions called chronic non-suppurative destructive cholangitis (CNSDC) in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. Macroautophagy (a major type of autophagy) is a process of cellular self-digestion that plays a critical role in energy homeostasis and in the cytoprotection to various stresses. Deregulated autophagy is thought to be associated with various human diseases. Key Messages: Accumulating evidences suggest that deregulated autophagy may be a central player in the pathogenesis of PBC. Damaged cholangiocytes involved in CNSDC show vesicular expression of autophagy marker LC3 and accumulation of p62/sequestosome-1, suggesting deregulated autophagy. Deregulated autophagy may be involved in the autoimmune process via the abnormal expression of mitochondrial antigens and also in cholangiocyte senescence in bile duct lesions in PBC. In vitro study showed that hydrophobic bile acids, such as glycochenodeoxycholic acid (GCDC), as well as serum deprivation and oxidative stress, cause autophagy, deregulated autophagy and abnormal expression of mitochondrial antigens followed by cellular senescence in cholangiocytes. Although exact mechanisms of deregulated autophagy remain to be clarified, endoplasmic reticulum (ER) stress may be a plausible cause of deregulated autophagy induced by GCDC in cholangiocytes. Impaired ‘biliary bicarbonate umbrella' may further exacerbate the toxicity of GCDC to cholangiocytes. Interestingly, pretreatment with ursodeoxycholic acid (UDCA) and tauro-UDCA, which is a chemical chaperone enhancing the adaptive capacity of the ER, significantly suppressed ER stress, deregulated autophagy and cellular senescence induced by GCDC and other stresses in cholangiocytes. Conclusions: GCDC may play a role in the occurrence of deregulated autophagy and cellular senescence at least partly through the induction of ER stress in PBC. Deregulated autophagy and cellular senescence can be a promising therapeutic target in PBC.

scholarly journals Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cirrhosis

2013 ◽  
Vol 67 (5) ◽  
pp. 396-402 ◽  
Author(s):  
Kenichi Harada ◽  
Yuko Kakuda ◽  
Yasunori Sato ◽  
Hiroko Ikeda ◽  
Shinji Shimoda ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Bile Duct ◽  
Primary Biliary Cirrhosis ◽  
Biliary Cirrhosis ◽  
Bile Duct Lesions
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