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Gut Liver. 2012 Jul;6(3):295-304. doi: 10.5009/gnl.2012.6.3.295. Epub 2012 May 2.

The crucial role of cholangiocytes in cholangiopathies.

Author information

  • Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Korea.

Abstract

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.

KEYWORDS:

Anti-fibrotic therapy; Cholangiopathies; Epithelial-mesenchymal interaction; Epithelial-mesenchymal transition

PMID:
22844556
[PubMed]
PMCID:
PMC3404165
Free PMC Article

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