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Sublytic C5b-9 induces IL-6 and TGF-β1 production by glomerular mesangial cells in rat Thy-1 nephritis through p300-mediated C/EBPβ acetylation.

FASEB J.2014 Mar;28(3):1511-25. Epub 2013 Dec 16
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摘要


CCAAT/enhancer-binding protein (C/EBPβ)-enhanced IL-6 and TGF-β1 promoter activity and p300-mediated C/EBPβ acetylation were involved in up-regulation of IL-6 and TGF-β1 expression in GMCs attacked by sublytic C5b-9. In detail, the elements of C/EBPβ binding to rat IL-6 and TGF-β1 promoter and 3 acetylated sites of rat C/EBPβ protein were first revealed. Furthermore, silencing the p300 or C/EBPβ gene in rat kidney significantly reduced the production of IL-6 and TGF-β1 and renal lesions in Thy-1N rats. Together, these data indicate that the mechanism of IL-6 and TGF-β1 production in renal tissue of Thy-1N rats is associated with sublytic C5b-9 up-regulated p300 and p300-mediated C/EBPβ acetylation as well as C/EBPβ-activated IL-6 and TGF-β1 genes.

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