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Two different phenotypes of cholangiocytes constitute the pathologic intrahepatic bile ducts of the PCK rat: Possible contribution of epithelial‐mesenchymal transition to progressive hepatic fibrosis
Author(s) -
Sato Yasunori,
Ozaki Satoru,
Harada Kenichi,
Nakanuma Yasuni
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1096
Subject(s) - vimentin , intrahepatic bile ducts , epithelial–mesenchymal transition , pathology , cholangiocyte , biology , cytokeratin , fibronectin , hepatic fibrosis , fibrosis , congenital hepatic fibrosis , hepatic stellate cell , immunohistochemistry , bile duct , medicine , transition (genetics) , cirrhosis , microbiology and biotechnology , extracellular matrix , portal hypertension , biochemistry , gene
Background The polycystic kidney (PCK) rat exhibits cystic dilations of intrahepatic bile ducts and progressive portal fibrosis, and is an animal model of Caroli□fs disease with congenital hepatic fibrosis. In liver sections of the PCK rat, two different types of intrahepatic bile ducts can be clearly recognized. That is, bile ducts lined by cuboidal‐shaped cholangiocytes (C‐type) and spindle‐shaped cholangiocytes (S‐type). Aim This study was perfomed to determine whether cholangiocytes of the PCK rat undergo epithelial‐mesenchymal transition (EMT), whereby contributes progressive portal fibrosis. Methods An immuonostaining was performed for paraffin‐embedded liver sections using primary antibodies against epithelial markers [cytokeratin (CK)19, E‐cadherin] and mesenchymal markers (vimentin, fibronectin). For in vitro experiments, cultured cholangiocytes of the PCK rat were incubated with transforming growth factor (TGF)‐beta1, and RT‐PCR analysis was performed for the markers. Results Immunohistochemically, CK19 and E‐cadherin were diffusely expressed in both C‐ and S‐types with reduced signal intensity in S‐type. S‐type showed positive immunoreactivity for vimentin and fibronectin, while C‐type was negative. In vitro, TGF‐beta1 strongly induced vimentin and fibronectin expression in the cholangiocytes. Conclusions This study provided evidence of possible occurrence of EMT in cholangiocytes of the PCK rat, which presumably participates in pregressive hepatic fibrosis.