Sasaki Motoko, Nakanuma Yasuni
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Int J Hepatol. 2012;2012:452143. doi: 10.1155/2012/452143. Epub 2011 Jul 7.
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.
原发性胆汁性肝硬化（PBC）的特征是患者血清中存在抗线粒体自身抗体（AMA），组织学上表现为小胆管慢性非化脓性破坏性胆管炎，最终导致广泛的胆管丢失和胆汁性肝硬化。胆管病变的自身免疫介导发病机制，包括AMA的意义、自身免疫过程的触发因素等仍不清楚。我们曾报道，胆管上皮细胞（BEC）中的细胞衰老可能与胆管病变有关，并且自噬可能先于PBC中胆管上皮衰老的过程。有趣的是，PBC中受损胆管的BEC表现出细胞衰老和自噬的特征。胆管上皮衰老的一个可疑致病因素是氧化应激。此外，衰老的BEC可能通过表达各种称为衰老相关分泌表型的趋化因子和细胞因子来调节胆管周围的微环境，并促成PBC的发病机制。
