[Epithelial-mesenchymal transition of biliary epithelial cells in advanced liver fibrosis].
The conversion of epithelial cells in a mesenchymal cell type is called "epithelial-mesenchymal-transition" (EMT). This process is defined by a loss of epithelial specific characteristics such as cell adhesion, polarity and a reorganization of cytoskeletal proteins. EMT has been shown to be involved in progression of cancer and in obstructive renal fibrosis. In this study we analyzed liver tissues in a bile-duct ligation model of rats and human liver biopsies with cholestatic fibrosis and chronic hepatitis c infection to determine if biliary epithelial cells undergo phenotypical and functional changes during chronic injury.


METHODS
Liver tissue of rats and human patients was examined by immunohistochemistry using antibodies against epithelial and mesenchymal specific targets as well as molecules of potentially activated signaling pathways. To study contribution of biliary epithelial cells in extracellular matrix production we performed laser microdissection combined with real-time PCR.


RESULTS
Bile duct ligation in rats induced a prominent biliary epithelial proliferation and a pronounced expression of vimentin was observed in biliary epithelial cells, whereas no vimentin expression was detectable in bile duct cells of sham operated rats. In human liver biopsies from patients with cholestatic fibrosis and chronic hepatitis c infection a prominent biliary expression of vimentin could be shown. Despite this, epithelial marker proteins were still detectable. Further, we observed collagen I mRNA expression in laser microdissected bile ducts.


CONCLUSIONS
Biliary epithelial cells show cytoskeletal rearrangements during chronic liver injury towards a mesenchymal phenotype. The detection of collagen I mRNA in bile duct cells suggests that they might participate in extracellular matrix production.
Schulze
F
F
Institut für Pathologie, Universitätsklinikum Köln.
Schardt
K
K
Wedemeyer
I
I
Konze
E
E
Wendland
K
K
Dirsch
O
O
Töx
U
U
Dienes
H P
HP
Odenthal
M
M
D000818:Animals; D002779:Cholestasis / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D004210:Dissection; D004847:Epithelial Cells / Q000473:pathology; D005704:Gallbladder / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology*; D008648:Mesoderm / Q000473:pathology*; D016133:Polymerase Chain Reaction; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology; D014746:Vimentin / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
D016212:Transforming Growth Factor beta; D014746:Vimentin; D051176:beta Catenin