当前位置： SCI文献检索 > JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY期刊下所有文献 > Statin pretreatment inhibits the lipopolysaccharide-induced epithelial-mesenchymal transition via the downregulation of toll-like receptor 4 and nuclear factor-κB in human biliary epithelial cells.

Statin pretreatment inhibits the lipopolysaccharide-induced epithelial-mesenchymal transition via the downregulation of toll-like receptor 4 and nuclear factor-κB in human biliary epithelial cells.

Abstract：

BACKGROUND AND AIM:Epithelial-mesenchymal transition (EMT) of biliary epithelial cells (BECs) plays an important role in biliary fibrosis. This study investigated the effects of simvastatin on the lipopolysaccharide (LPS)-induced EMT and related signal pathways in BECs. METHODS:Biliary epithelial cells were exposed to LPS (2 µg/mL) or transforming growth factor β1 (TGF-β1) (5 ng/mL) for 5 days. The EMT was assessed by a gain of mesenchymal cell markers (vimentin, N-cadherin, slug, and Twist-1) and a loss of epithelial cell markers (E-cadherin). The effects of simvastatin on the EMT induced by LPS or TGF-β1 were determined by the changes in the levels of EMT markers and TLR4 and in the c-Jun N-terminal kinase (JNK), p38, and nuclear factor-κB (NF-κB) signaling pathways. RESULTS:Compared with the BECs treated with LPS alone, co-treatment with simvastatin and LPS induced an increase in the expression of E-cadherin and decreases in the expression levels of mesenchymal cell markers. The LPS-induced TLR4 expression level was slightly decreased by co-treatment with simvastatin. LPS-induced BEC growth was markedly inhibited by co-treatment with simvastatin. Furthermore, pretreatment with simvastatin inhibited the LPS-induced EMT in BECs by downregulating NF-κB and JNK phosphorylation. The suppressive effects of simvastatin pretreatment on the induction of the EMT by TGF-β1 were also demonstrated in H69 cells. CONCLUSIONS:Our results demonstrate that LPS or TGF-β1 promote the EMT in BECs that that pretreatment with simvastatin inhibited the induced EMT by downregulating toll-like receptor 4 and NF-κB phosphorylation. This finding suggests that simvastatin can be considered a new agent for preventing biliary fibrosis associated with the EMT of BECs.

journal_name

J Gastroenterol Hepatol

journal_title

Journal of gastroenterology and hepatology

authors

Kim Y,Lee EJ,Jang HK,Kim CH,Kim DG,Han JH,Park SM

doi

10.1111/jgh.13230

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

1220-8

issue

eissn

0815-9319

issn

1440-1746

journal_volume

pub_type

杂志文章

在线工具

Statin pretreatment inhibits the lipopolysaccharide-induced epithelial-mesenchymal transition via the downregulation of toll-like receptor 4 and nuclear factor-κB in human biliary epithelial cells.