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• W1553047343 endingPage "1425" @default.
• W1553047343 startingPage "1418" @default.
• W1553047343 abstract "Abstract Background/Aims: Liver injury results in the activation of hepatic stellate cells (HSCs), which in turn produce matrix metalloproteinase (MMP) in response to pro‐inflammatory cytokines for tissue remodelling. This study explored the transcriptional induction of the MMP‐1 gene by tumour necrosis factor‐α (TNF‐α) in HSCs. Methods: The LI90 human HSC line was used in the present study. Gelatin zymography, enzyme‐linked immunosorbent assay, Northern blotting and gene promoter–reporter assays were used to analyse the induction of MMP‐1 protein, mRNA expression and gene transcription respectively. Deletional or site‐directed mutations were introduced into the promoter region and transiently transfected into LI90 cells to determine the cis ‐acting elements necessary for TNF‐α inducibility. Gel shift mobility assays were used to determine the transcriptional factors involved in the TNF‐α responsiveness. Results: TNF‐α upregulated MMP‐1 protein and mRNA expression in a dose‐dependent manner. A time–course experiment revealed a rapid induction of MMP‐1 mRNA expression after TNF‐α treatment. Mutation in a putative nuclear factor (NF)‐κB‐binding site at −2541 bp almost completely abolished the TNF‐α response to MMP‐1 gene‐promoter activity, suggesting transcriptional regulation of MMP‐1 expression by TNF‐α via this site. Electrophoretic mobility shift assay and supershift assays indicated that this transcriptional regulation was regulated via the p50/p50 homodimer of NF‐κB. Conclusions: MMP‐1 gene expression might be induced by TNF‐α via the p50/p50 homodimer of NF‐κB in activated human HSCs." @default.
• W1553047343 created "2016-06-24" @default.
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• W1553047343 date "2008-10-10" @default.
• W1553047343 modified "2023-10-16" @default.
• W1553047343 title "Induction of matrix metalloproteinase-1 gene transcription by tumour necrosis factor α via the p50/p50 homodimer of nuclear factor-κ B in activated human hepatic stellate cells" @default.
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• W1553047343 doi "https://doi.org/10.1111/j.1478-3231.2008.01883.x" @default.
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