Abstract
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.
Highlights
Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that affects usually middle-aged women and occasionally leads to liver failure and liver transplantation [1,2,3,4,5]
Autoimmune pathogenesis is suggested in PBC [1,2,3,4], because PBC is serologically characterized by a high titer of serum antimitochondrial autoantibodies (AMAs) and by an increased level of immunoglobulin M (IgM)
We have shown that the expression of CCL2 and CX3CL1 was significantly higher in biliary epithelial cells (BECs) in inflamed and damaged small bile ducts in PBC, than in noninflamed bile ducts and control livers
Summary
Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that affects usually middle-aged women and occasionally leads to liver failure and liver transplantation [1,2,3,4,5]. The most accepted hypothesis states that PBC results from a combination of multiple genetic factors (susceptible genetic background) and superimposed environmental triggers In this scenario, adaptive, both humoral and cellular (CD4 and CD8 T cells), and innate immunity have been proposed as coplayers in immune-mediated liver damage; the etiology and pathogenesis of PBC remain unclear. We have recently reported that cellular senescence and autophagy may be involved in bile duct lesions in PBC [24,25,26,27,28] These two cellular processes may be related to autoimmune mechanism such as AMAs and the autoantigenspecific T cell and play a role to cause autoimmune-mediated. We will focus on cellular senescence and autophagy in BECs in PBC and their possible involvement in the progression of diseases
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