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• W2024160852 abstract "TGF-β (transforming growth factor-β) plays a critical role in modulating the inflammatory response and other biological processes through its regulation of the production of MMPs (matrix metalloproteinases). In both Mono-Mac-6 and RAW264.7 monocyte/macrophage cells, TGF-β abrogated lipopolysaccharide-induced increases in the enzymic activity and mRNA level of MMP-9. A fragment of the human MMP-9 promoter was used to characterize its regulation by TGF-β signalling. In RAW264.7 cells, TGF-β or its downstream signalling protein, Smad3 (Sma- and Mad-related protein 3), inhibited lipopolysaccharide-stimulated promoter activity. The suppressive activity of TGF-β on the MMP-9 promoter was abrogated by an inhibitory Smad, Smad7. The MMP-9 promoter contains a putative TIE (TGF-β inhibitory element). However, neither mutation nor deletion of the TIE had any effect on the inhibitory activity of TGF-β on MMP-9 transcription, indicating that the consensus TIE is not required for this effect of TGF-β. Analysis using a series of deletion mutants of the MMP-9 promoter revealed that a region containing a consensus NF-κB (nuclear factor-κB) site is required for the basal activity and TGF-β-mediated suppression of the promoter. Mutation of the putative NF-κB site not only markedly reduced the basal transcriptional activity of the promoter, but also abrogated the responsiveness of the promoter to TGF-β. In addition, a minimal promoter containing one copy of the NF-κB sequence was responsive to TGF-β treatment. Furthermore, an electrophoretic mobility shift assay was performed with the nuclear extracts from RAW264.7 cells, and it was found that TGF-β treatment did not disrupt the binding of NF-κB p50 and p65 proteins to the NF-κB sequence. Taken together, these studies indicate that the NF-κB site is indispensable for the suppressive activity of TGF-β in the regulation of MMP-9 transcription." @default.
• W2024160852 created "2016-06-24" @default.
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• W2024160852 date "2004-07-06" @default.
• W2024160852 modified "2023-09-25" @default.
• W2024160852 title "Suppression of matrix metalloproteinase-9 transcription by transforming growth factor-β is mediated by a nuclear factor-κB site" @default.
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• W2024160852 doi "https://doi.org/10.1042/bj20040058" @default.
• W2024160852 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1133847" @default.
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