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- W2028793815 abstract "J. Neurochem. (2010) 113 , 1133–1149. Abstract The bioactivity of endothelin‐1 (ET‐1) has been suggested in the development of CNS diseases, including disturbance of water homeostasis and blood‐brain barrier integrity. Recent studies suggest that hypoxic/ischemic injury of the brain induces release of ET‐1, behaving through a G‐protein coupled ET receptor family. The deleterious effects of ET‐1 on astrocytes may aggravate brain inflammation. Increased plasma levels of matrix metalloproteinases (MMPs), in particular MMP‐9, have been observed in patients with neuroinflammatory disorders. However, the detailed mechanisms underlying ET‐1‐induced MMP‐9 expression remain unknown. In this study, the data obtained with zymographic, western blotting, real‐time PCR, and immunofluorescent staining analyses showed that ET‐1‐induced MMP‐9 expression was mediated through an ET B ‐dependent transcriptional activation. Engagement of G i/o ‐ and G q ‐coupled ET B receptor by ET‐1 led to activation of p42/p44 MAPK and then activated transcription factors including Ets‐like kinase, nuclear factor‐kappa B, and activator protein‐1 (c‐ Jun /c‐ Fos ). These activated transcription factors translocated into nucleus and bound to their corresponding binding sites in MMP‐9 promoter, thereby turning on MMP‐9 gene transcription. Eventually, up‐regulation of MMP‐9 by ET‐1 enhanced the migration of astrocytes. Taken together, these results suggested that in astrocytes, activation of Ets‐like kinase, nuclear factor‐kappa B, and activator protein‐1 by ET B ‐dependent p42/p44 MAPK signaling is necessary for ET‐1‐induced MMP‐9 gene up‐regulation. Understanding the mechanisms of MMP‐9 expression and functional changes regulated by ET‐1/ET B system on astrocytes may provide rational therapeutic interventions for brain injury associated with increased MMP‐9 expression." @default.
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- W2028793815 date "2010-05-04" @default.
- W2028793815 modified "2023-10-16" @default.
- W2028793815 title "Endothelin-1 enhances cell migration via matrix metalloproteinase-9 up-regulation in brain astrocytes" @default.
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- W2028793815 doi "https://doi.org/10.1111/j.1471-4159.2010.06680.x" @default.
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