J Korean Med Sci.  2010 Jul;25(7):1066-1070. 10.3346/jkms.2010.25.7.1066.

Epithelial-Mesenchymal Transitions of Bile Duct Epithelial Cells in Primary Hepatolithiasis

• Zhao L
• Yang R
• Cheng L
• Wang M
• Jiang Y
• Wang S

• KMID: 1792958
• DOI: http://doi.org/10.3346/jkms.2010.25.7.1066

Abstract

The purpose of this study was to explore the role of epithelial-mesenchymal transition in the pathogenesis of hepatolithiasis. Thirty-one patients with primary hepatolithiasis were enrolled in this study. Expressions of E-cadherin, alpha-catenin, alpha-SMA, vimentin, S100A4, TGF-beta1 and P-smad2/3 in hepatolithiasis bile duct epithelial cells were examined by immunohistochemistry staining. The results showed that the expressions of the epithelial markers E-cadherin and alpha-catenin were frequently lost in hepatolithiasis (32.3% and 25.9% of cases, respectively), while the mesenchymal markers vimentin, alpha-SMA and S100A4 were found to be present in hepatolithiasis (35.5%, 29.0%, and 32.3% of cases, respectively). The increased mesenchymal marker expression was correlated with decreased epithelial marker expression. The expressions of TGF-beta1 and P-smad2/3 in hepatolithiasis were correlated with the expression of S100A4. These data indicate that TGF-beta1-mediated epithelial-mesenchymal transition might be involved in the formation of hepatolithiasis.

Keyword

Epithelial-mesenchymal Transition; Primary Hepatolithiasis; Bile Duct Epithelial Cell; Transforming Growth Factor beta1; Immunohistochemistry

MeSH Terms

Adult
*Bile Ducts/cytology/metabolism/pathology
Biological Markers/*metabolism
Cell Differentiation/*physiology
Epithelial Cells/cytology/*physiology
Epithelium/physiology
Female
*Gallstones/metabolism/pathology
Humans
Liver Diseases/metabolism/*pathology
Male
Mesoderm/cytology/*physiology
Middle Aged

Figure

• 

  Fig. 1 Histopathological assessment of HL. Histopathological assessment (hematoxylin-eosin staining) of samples from (A) control group and (B) primary hepatolithiasis, abnormalities in which include infiltrating inflammatory cells in portal areas, fibrous tissue hyperplasia, biliary dilatation, and necrosis. Magnification ×200.

• 

  Fig. 2 Immunohistochemical assessment of epithelial and mesenchymal markers. Expressions of the epithelial markers (A) E-cadherin and (B) α-catenin in primary hepatolithiasis. Some BECs lost expression of epithelial markers (arrows). Expressions of mesenchymal markers (C) Vimentin, (D) α-SMA and (E) S100A4 in the liver bile ducts in hepatolithiasis. Note the brown staining of the markers lining the plasma membrane and in the cytoplasm (arrows). In normal liver tissue, S100A4 is neganative (F). Magnification ×400.

• 

  Fig. 3 Immunohistochemical assessment of TGF-β1 and P-smad2/3. (A) TGF-β1 expressed in the cytoplasm and on the plasma membrane of bile duct epithelial cells in hepatolithiasis, and (B) P-smad2/3 accumulated in the nucleus of bile duct epithelial cells in hepatolithiasis. Magnification ×400.

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