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• W4328137153 endingPage "103848" @default.
• W4328137153 startingPage "103848" @default.
• W4328137153 abstract "Astrocytes are key players in neuroinflammation. In response to central nervous system (CNS) injury or disease, astrocytes undergo reactive astrogliosis, which is characterized by increased proliferation, migration, and glial fibrillary acidic protein (GFAP) expression. Activation of the transcription factor nuclear factor-κB (NF-κB) and upregulation of downstream proinflammatory mediators in reactive astrocytes induce a proinflammatory phenotype in astrocytes, thereby exacerbating neuroinflammation by establishing an inflammatory loop. In this study, we hypothesized that excessive fibronectin (FN) derived from reactive astrocytes would induce this proinflammatory phenotype in astrocytes in an autocrine manner. We exogenously treated astrocytes with monomer FN, which can be incorporated into the extracellular matrix (ECM), to mimic plasma FN extravasated through a compromised blood-brain barrier in neuroinflammation. We also induced de novo synthesis and accumulation of astrocyte-derived FN through tumor necrosis factor-α (TNF-α) stimulation. The excessive FN deposition resulting from both treatments initiated reactive astrogliosis and triggered NF-κB signaling in the cultured astrocytes. In addition, inhibition of FN accumulation in the ECM by the FN inhibitor pUR4 strongly attenuated the FN- and TNF-α-induced GFAP expression, NF-κB activation, and proinflammatory mediator production of astrocytes by interrupting FN-β1 integrin coupling and thus the inflammatory loop. In an in vivo experiment, intrathecal injection of pUR4 considerably ameliorated FN deposition, GFAP expression, and NF-κB activation in inflamed spinal cord, suggesting the therapeutic potential of pUR4 for attenuating neuroinflammation and promoting neuronal function restoration." @default.
• W4328137153 created "2023-03-22" @default.
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• W4328137153 date "2023-06-01" @default.
• W4328137153 modified "2023-10-17" @default.
• W4328137153 title "Astrocyte-associated fibronectin promotes the proinflammatory phenotype of astrocytes through β1 integrin activation" @default.
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• W4328137153 doi "https://doi.org/10.1016/j.mcn.2023.103848" @default.
• W4328137153 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36948232" @default.
• W4328137153 hasPublicationYear "2023" @default.
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