Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Korea.
Gut Liver. 2012 Jul;6(3):295-304. doi: 10.5009/gnl.2012.6.3.295. Epub 2012 May 2.
Cholangiopathies are diseases involving the intrahepatic biliary tree. They appear to involve, chronic inflammation of the bile ducts, which can lead to the development of bile duct cholestasis, proliferation/ductopenia, biliary fibrosis, and malignant transformation. Sustained stimulatory insults to biliary epithelial cells can induce a ductular reaction, which has a key role in the initiation and progression of cholangiopathies. The epithelial-mesenchymal interaction between reactive cholangiocytes and mesenchymal cells with the inflammatory infiltrates plays a major role in this pathogenesis. Cytokines, chemokines, growth factors and morphogens mediate these interactions in an autocrine or paracrine manner. The main hepatic myofibroblasts (MFs) in cholangiopathies originate from portal fibroblasts. Hepatic stellate cells and fibrocytes also transform into MFs. Whether cholangiocytes or hepatocytes are a source of MFs via the epithelial-mesenchymal transition (EMT) remains a matter of controversy. Although there have been numerous indirect findings supporting the theory of a cholangiocyte EMT in human tissues, recent studies using lineage tracing methods have demonstrated strong evidence against the EMT. Understanding the pathogenic mechanisms involved in cholangiopathies can allow for better-targeted anti-fibrotic therapies in animal models. Before anti-fibrotic therapies can translate into clinical trials, improved monitoring of the fibrotic progression of cholangiopathies and an accurate assessment regarding the effectiveness of the proposed treatments must be achieved.
胆管疾病是涉及肝内胆管的疾病。它们似乎涉及胆管的慢性炎症，这可能导致胆管胆汁淤积、增殖/胆管减少、胆管纤维化和恶性转化的发展。持续的胆管上皮细胞刺激可以诱导胆管反应，这在胆管疾病的发生和进展中起着关键作用。反应性胆管细胞与炎症浸润的间充质细胞之间的上皮-间充质相互作用在这种发病机制中起着主要作用。细胞因子、趋化因子、生长因子和形态发生素以自分泌或旁分泌的方式介导这些相互作用。胆管疾病中的主要肝肌成纤维细胞 (MFs) 来源于门脉成纤维细胞。肝星状细胞和成纤维细胞也可转化为 MFs。胆管细胞或肝细胞是否通过上皮-间充质转化 (EMT) 成为 MFs 的来源仍存在争议。尽管有许多间接发现支持人类组织中胆管细胞 EMT 的理论，但最近使用谱系追踪方法的研究提供了强有力的证据反对 EMT。了解胆管疾病中涉及的发病机制可以在动物模型中实现更有针对性的抗纤维化治疗。在抗纤维化治疗可以转化为临床试验之前，必须改进对胆管疾病纤维化进展的监测，并对拟议治疗的有效性进行准确评估。
