Journal
JOURNAL OF SURGICAL RESEARCH
Volume 171, Issue 2, Pages 819-825Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jss.2010.04.059
Keywords
transdifferentiation; Smad2/3; transforming growth factor beta 1; lipopolysaccharides
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Funding
- Science and Technology Foundation of Guizhou Province [2009GZ14798]
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Background. Recent studies have revealed that the epithelial-mesenchymal transition (EMT) of bile duct epithelial cells is engaged in hepatic fibrogenesis. However, the association between etiological factors of liver disease such as virus or bacterial infection and EMT remains to be investigated. The present study focuses on the inductive role of endotoxin, the main component of the cell wall's ectoblast of gram-negative bacteria, in the EMT of human intrahepatic biliary epithelial cells (HIBEpiCs). Methods. The expressions of E-cadherin, S100A4, alpha-SMA, TGF-beta 1, and Smad2/3 in HIBEpiCs cultured with or without lipopolysaccharide LPS, were detected by real-time PCR and Western blotting. We blocked the expression of TGF-beta 1 using paclitaxel and knocked down Smad2/3 by siRNA to explore the role of TGF-beta 1/Smad2/3 pathway in the EMT of HIBEpiCs. Results. Resting HIBEpiCs showed epithelioid cobblestone morphology, and underwent a phenotypic change to produce bipolar cells with a fibroblastic morphology when co-cultured with LPS. After LPS stimulation and the up-regulation of mRNA and protein expression of TGF-b1 and Smad2/Smad3, the mRNA and protein expression of mesenchymal markers (S100A and alpha-SMA) increased significantly. Paclitaxel inhibited the mRNA and protein expression of TGF-beta(1) in vitro. Knock-down of Smad2/3 by siRNA led to up-regulation of epithelial markers E-cadherin and down-regulation of S100A and alpha-SMA, indicating a reversal of the EMT. Conclusions. LPS can induce the expression of TGF-beta 1 and a subsequent EMT in HIBEpiCs, and the inhibition of TGF-beta 1 or Smad 2/3 could reverse this EMT, suggesting that LPS may play a potential role in the EMT of HIBEpiCs. (C) 2011 Elsevier Inc. All rights reserved.
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