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Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Promotes Hepatic Stellate Cells Migration via Canonical NF-κB/MMP9 Pathway.

Authors :
Xu, Mingcui
Zhang, Feng
Wang, Aixiu
Wang, Chen
Cao, Yu
Zhang, Ming
Zhang, Mingming
Su, Min
Zou, Xiaoping
Xu, Guifang
Zhuge, Yuzheng
Source :
PLoS ONE; 12/1/2016, Vol. 11 Issue 12, p1-14, 14p
Publication Year :
2016

Abstract

In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) have mainly been assessed in association with liver regeneration. However, the effects of TWEAK on liver fibrosis have not been fully elucidated. To investigate the effects of TWEAK on human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms, human HSCs line—LX-2 were cultured with TWEAK. Cell migration was detected by transwell assay; cell viability was evaluated by Cell Counting Kit-8; the expression of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 gene was identified by quantitative real-time polymerase chain reaction and western blotting; the activity of matrix metalloproteinases (MMPs) was tested by enzyme-linked immuno sorbent assay; small interfering RNA transfection was applied for depletion of MMP9 and p65. The result of transwell assay revealed that TWEAK promoted LX-2 migration. Subsequently, our data testified that the expression and activity of MMP9 was induced by TWEAK in LX-2 cells, which enhanced the migration. Furthermore, our findings showed that TWEAK upregulated the phosphorylation of IκBα and p65 protein to increase MMP9 expression in LX-2 cells. Meanwhile, the alpha-smooth muscle actin, vimentin and desmin expression were upregulated following TWEAK treatment. The results in the present study revealed that TWEAK promotes HSCs migration via canonical NF-κB/MMP9 pathway, which possibly provides a molecular basis targeting TWEAK for the therapy of liver fibrosis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
11
Issue :
12
Database :
Complementary Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
119867637
Full Text :
https://doi.org/10.1371/journal.pone.0167658