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

亚溶解性 C5b-9 通过 p300 介导的 C/EBPβ 乙酰化诱导大鼠 Thy-1 肾炎肾小球系膜细胞产生 IL-6 和 TGF-β1

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作者:Jing Zhang, Yan Li, Kai Shan, Lulu Wang, Wen Qiu, Yanlai Lu, Dan Zhao, Ganqian Zhu, Fengxia He, Yingwei Wang

Abstract

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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