亚溶血性 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。
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.
机构信息
1Department of Microbiology and Immunology, Nanjing Medical University, Hanzhong Rd. 140, Nanjing, Jiangsu 210029, China.
出版信息
FASEB J. 2014 Mar;28(3):1511-25. doi: 10.1096/fj.13-242693. Epub 2013 Dec 16.
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.
CCAAT/增强子结合蛋白（C/EBPβ）增强了 IL-6 和 TGF-β1 启动子的活性，并且 p300 介导的 C/EBPβ乙酰化参与了亚溶血性 C5b-9 攻击的肾小球系膜细胞中 IL-6 和 TGF-β1 表达的上调。具体而言，首次揭示了 C/EBPβ 与大鼠 IL-6 和 TGF-β1 启动子结合的元件以及大鼠 C/EBPβ 蛋白的 3 个乙酰化位点。此外，沉默大鼠肾脏中的 p300 或 C/EBPβ 基因可显著减少 Thy-1N 大鼠中 IL-6 和 TGF-β1 的产生和肾脏损伤。综上所述，这些数据表明，Thy-1N 大鼠肾组织中 IL-6 和 TGF-β1 产生的机制与亚溶血性 C5b-9 上调的 p300 和 p300 介导的 C/EBPβ 乙酰化以及 C/EBPβ 激活的 IL-6 和 TGF-β1 基因有关。
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