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• W2116596367 abstract "Transforming growth factor-β (TGF-β) and matrix metalloproteinases (MMPs) are the multifunctional factors during diverse physiological and pathological processes including development, wound healing, proliferation, and cancer metastasis. Both TGF-β and MMPs have been shown to play crucial roles in brain pathological changes. Thus, we investigated the molecular mechanisms underlying TGF-β1-induced MMP-9 expression in brain astrocytes.Rat brain astrocytes (RBA-1) were used. MMP-9 expression was analyzed by gelatin zymography and RT-PCR. The involvement of signaling molecules including MAPKs and NF-κB in the responses was investigated using pharmacological inhibitors and dominant negative mutants, determined by western blot and gene promoter assay. The functional activity of MMP-9 was evaluated by cell migration assay.Here we report that TGF-β1 induces MMP-9 expression and enzymatic activity via a TGF-β receptor-activated reactive oxygen species (ROS)-dependent signaling pathway. ROS production leads to activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun-N-terminal kinase (JNK) and then activation of the NF-κB transcription factor. Activated NF-κB turns on transcription of the MMP-9 gene. The rat MMP-9 promoter, containing a NF-κB cis-binding site, was identified as a crucial domain linking to TGF-β1 action.Collectively, in RBA-1 cells, activation of ERK1/2- and JNK-NF-κB cascades by a ROS-dependent manner is essential for MMP-9 up-regulation/activation and cell migration induced by TGF-β1. These findings indicate a new regulatory pathway of TGF-β1 in regulating expression of MMP-9 in brain astrocytes, which is involved in physiological and pathological tissue remodeling of central nervous system." @default.
• W2116596367 created "2016-06-24" @default.
• W2116596367 creator A5024243656 @default.
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• W2116596367 creator A5046825149 @default.
• W2116596367 creator A5061974988 @default.
• W2116596367 creator A5089893818 @default.
• W2116596367 date "2010-12-01" @default.
• W2116596367 modified "2023-09-26" @default.
• W2116596367 title "Transforming growth factor-β1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-κB pathways" @default.
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• W2116596367 doi "https://doi.org/10.1186/1742-2094-7-88" @default.
• W2116596367 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3002339" @default.
• W2116596367 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21134288" @default.
• W2116596367 hasPublicationYear "2010" @default.
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