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, α-SMA, TGF-β1, 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-β1 using paclitaxel and knocked down Smad2/3
by siRNA to explore the role of TGF-β1/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-β1 and Smad2/Smad3, the mRNA and protein expression of mesenchymal markers (S100A
and α-SMA) increased significantly. Paclitaxel inhibited the mRNA and protein expression
of TGF-β1 in vitro. Knock-down of Smad2/3 by siRNA led to up-regulation of epithelial markers E-cadherin
and down-regulation of S100A and α-SMA, indicating a reversal of the EMT.
Conclusions
LPS can induce the expression of TGF-ß1 and a subsequent EMT in HIBEpiCs, and the
inhibition of TGF-ß1 or Smad 2/3 could reverse this EMT, suggesting that LPS may play
a potential role in the EMT of HIBEpiCs.
Key Words
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References
- Portal tract fibrogenesis in the liver.Lab Invest. 2004; 84: 153
- Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation.Am J Pathol. 2006; 168: 1500
- Cholangiocytes with mesenchymal features contribute to progressive hepatic fibrosis of the polycystic kidney rat.Am J Pathol. 2007; 171: 1859
- Epithelial-mesenchymal transition contributes to portal tract fibrogenesis during human chronic liver disease.Lab Invest. 2008; 88: 112
- Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans.J Clin Invest. 2008; 118: 3331
- TGF-β and epithelial-to-mesenchymal transitions.Oncogene. 2005; 24: 5764
- Epithelial to mesenchymal transition in renal fibrogenesis: Pathologic significance, molecular mechanism, and therapeutic intervention.J Am Soc Nephrol. 2004; 15: 1
- Paclitaxel interrupts TGF-β 1 signaling between gallbladder epithelial cells and myofibroblasts.J Surg Res. 2007; 141: 183
- Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-β as major players and therapeutic targets.J Cell Mol Med. 2006; 10: 76
- Smad proteins and transforming growth factor-β signaling.Kidney Int Suppl. 2000; 77: S45
- New insights into TGF-β-Smad signalling.Trends Biochem Sci. 2004; 29: 265
- Progression of chronic renal failure.Arch Intern Med. 2003; 163: 1417
- BMP-7 counteracts TGF-β1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury.Nat Med. 2003; 9: 964
- Chronic renal allograft dysfunction: The role of T cell-mediated tubular epithelial to mesenchymal cell transition.J Am Soc Nephrol. 2004; 15: 390
- Chronic allograft nephropathy: Intraepithelial signals generated by transforming growth factor-β and bone morphogenetic protein-7.Am J Transplant. 2006; 6: 1367
- Biliary epithelial-mesenchymal transition in posttransplantation recurrence of primary biliary cirrhosis.Hepatology. 2007; 45: 977
Article info
Publication history
Published online: May 31, 2010
Received:
September 28,
2009
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
