期刊
HUMAN PATHOLOGY
卷 39, 期 1, 页码 102-115出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2007.05.021
关键词
FSP1; HSP47; myofibroblast; primary biliary cirrhosis; vimentin
类别
资金
- NIDDK NIH HHS [R01 DK58123, P30 DK50306, T32 DK07066] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK050306, T32DK007066, R01DK058123] Funding Source: NIH RePORTER
The epithelial to mesenchymal transition has recently been implicated as a source of fibrogenic myofibroblasts in organ fibrosis, particularly in the kidney. There is as yet minimal evidence for the epithelial to mesenchymal transition in the liver. We hypothesized that this process in biliary epithelial cells plays an important role in biliary fibrosis and might be found in patients with especially rapid forms, such as is seen in biliary atresia. We therefore obtained liver tissue from patients with biliary atresia as well as a variety of other pediatric and adult liver diseases. Tissues were immunostained with antibodies against the biliary epithelial cell marker CK19 as well as with antibodies against proteins characteristically expressed by cells undergoing the epithelial to mesenchymal transition, including fibroblast-specific protein 1, the collagen chaperone heat shock protein 47, the intermediate filament protein vimentin, and the transcription factor Snail. The degree of colocalization was quantified using a multispectral imaging system. We observed significant colocalization between CK19 and other markers of the epithelial to mesenchymal transition in biliary atresia as well as other liver diseases associated with significant bile ductular proliferation, including primary biliary cirrhosis. There was minimal colocalization seen in healthy adult and pediatric livers, or in livers not also demonstrating bile ductular proliferation. Multispectral imaging confirmed significant colocalization of the different markers in biliary atresia. In conclusion, we present significant histologic evidence suggesting that the epithelial to mesenchymal transition occurs in human liver fibrosis, particularly in diseases such as biliary atresia and primary biliary cirrhosis with prominent bile ductular proliferation. (c) 2008 Elsevier Inc. All rights reserved.
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