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LPS-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells.
J Surg Res. 2011 Dec; 171(2):819-25.JS

Abstract

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-β1 and a subsequent EMT in HIBEpiCs, and the inhibition of TGF-β1 or Smad 2/3 could reverse this EMT, suggesting that LPS may play a potential role in the EMT of HIBEpiCs.

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Authors+Show Affiliations

Zhao L
Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China.
Yang R
No affiliation info available
Cheng L
No affiliation info available
Wang M
No affiliation info available
Jiang Y
No affiliation info available
Wang S
No affiliation info available

MeSH

ActinsAntineoplastic Agents, PhytogenicBiliary TractCadherinsCell LineEpithelial CellsEpithelial-Mesenchymal TransitionHumansLipopolysaccharidesPaclitaxelRNA, MessengerRNA, Small InterferingS100 ProteinsSignal TransductionSmad2 ProteinSmad3 ProteinTransforming Growth Factor beta1

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20691985

Citation

Zhao, Lijin, et al. "LPS-induced Epithelial-mesenchymal Transition of Intrahepatic Biliary Epithelial Cells." The Journal of Surgical Research, vol. 171, no. 2, 2011, pp. 819-25.
Zhao L, Yang R, Cheng L, et al. LPS-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells. J Surg Res. 2011;171(2):819-25.
Zhao, L., Yang, R., Cheng, L., Wang, M., Jiang, Y., & Wang, S. (2011). LPS-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells. The Journal of Surgical Research, 171(2), 819-25. https://doi.org/10.1016/j.jss.2010.04.059
Zhao L, et al. LPS-induced Epithelial-mesenchymal Transition of Intrahepatic Biliary Epithelial Cells. J Surg Res. 2011;171(2):819-25. PubMed PMID: 20691985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LPS-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells. AU - Zhao,Lijin, AU - Yang,Rigao, AU - Cheng,Long, AU - Wang,Maijian, AU - Jiang,Yan, AU - Wang,Shuguang, Y1 - 2010/05/26/ PY - 2009/09/28/received PY - 2010/04/16/revised PY - 2010/04/29/accepted PY - 2010/8/10/entrez PY - 2010/8/10/pubmed PY - 2012/1/10/medline SP - 819 EP - 25 JF - The Journal of surgical research JO - J Surg Res VL - 171 IS - 2 N2 - 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-β1 and a subsequent EMT in HIBEpiCs, and the inhibition of TGF-β1 or Smad 2/3 could reverse this EMT, suggesting that LPS may play a potential role in the EMT of HIBEpiCs. SN - 1095-8673 UR - https://www.unboundmedicine.com/medline/citation/20691985/LPS_induced_epithelial_mesenchymal_transition_of_intrahepatic_biliary_epithelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(10)00446-4 DB - PRIME DP - Unbound Medicine ER -