Sublytic C5b-9 triggers glomerular mesangial cell apoptosis via XAF1 gene activation mediated by p300-dependent IRF-1 acetylation.
Sublytic C5b-9 triggers glomerular mesangial cell apoptosis via XAF1 gene activation mediated by p300-dependent IRF-1 acetylation.
复制标题
Sublytic C5b-9 通过 p300 依赖性 IRF-1 乙酰化介导的 XAF1 基因激活触发肾小球系膜细胞凋亡。
DOI：
10.1038/cddis.2014.153
复制
发表时间：
2014-04-17
影响因子：
9
通讯作者：
Wang, Y.
中科院分区：
文献类型：
--
作者：
Qiu, W.;Zhou, J.;Zhu, G.;Zhao, D.;He, F.;Zhang, J.;Lu, Y.;Yu, T.;Liu, L.;Wang, Y.
关键词：
大鼠 Thy-1 肾炎 (Thy-1N)（人类系膜增生性肾炎 (MsPGN) 模型）中肾小球系膜细胞 (GMC) 的凋亡伴随着亚溶解性 C5b-9 沉积。然而，亚裂解C5b-9诱导GMC凋亡的机制尚不清楚。在本研究中，确定了 X 连锁凋亡相关抑制剂 (XAF1) 表达对 GMC 凋亡的影响，以及 p300 和干扰素调节因子 1 (IRF-1) 在介导 XAF1 基因激活中的作用，无论是在 C5b-9 诱导的 GMC（体外）还是 Thy-1N 大鼠的肾组织（体内）中。体外研究表明，IRF-1 增强的 XAF1 基因激活及其通过 p300 介导的 IRF-1 乙酰化的调节参与了 Sublytic C5b-9 诱导的 GMC 凋亡。还揭示了 IRF-1 与 XAF1 启动子结合的元件以及 IRF-1 蛋白的两个乙酰化位点。在体内，肾组织中 p300、IRF-1 或 XAF1 基因的沉默减少了 Thy-1N 大鼠的 GMC 凋亡和继发性 GMC 增殖以及尿蛋白分泌。总之，这些数据表明，亚裂解 C5b-9 诱导 p300 和 IRF-1 的表达，以及 p300 依赖性 IRF-1 乙酰化，这可能有助于 Thy-1N 大鼠中 XAF1 基因激活和随后的 GMC 凋亡。
The apoptosis of glomerular mesangial cells (GMCs) in rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis (MsPGN), is accompanied by sublytic C5b-9 deposition. However, the mechanism by which sublytic C5b-9 induces GMC apoptosis is unclear. In the present studies, the effect of X-linked inhibitor of apoptosis-associated factor 1 (XAF1) expression on GMC apoptosis and the role of p300 and interferon regulatory factor-1 (IRF-1) in mediating XAF1 gene activation were determined, both in the GMCs induced by sublytic C5b-9 (in vitro) and in the renal tissues of rats with Thy-1N (in vivo). The in vitro studies demonstrated that IRF-1-enhanced XAF1 gene activation and its regulation by p300-mediated IRF-1 acetylation were involved in GMC apoptosis induced by sublytic C5b-9. The element of IRF-1 binding to XAF1 promoter and two acetylated sites of IRF-1 protein were also revealed. In vivo, silence of p300, IRF-1 or XAF1 genes in the renal tissues diminished GMC apoptosis and secondary GMC proliferation as well as urinary protein secretion in Thy-1N rats. Together, these data implicate that sublytic C5b-9 induces the expression of both p300 and IRF-1, as well as p300-dependent IRF-1 acetylation that may contribute to XAF1 gene activation and subsequent GMC apoptosis in Thy-1N rats.
登录
查看更多内容
影响因子：
19.6
作者：
Couser, WG;Pippin, JW;Shankland, SJ
通讯作者：
Shankland, SJ
影响因子：
5.6
作者：
Kim, Dae Hyun;Kim, Ji Min;Chung, Hae Young
通讯作者：
Chung, Hae Young
影响因子：
9.8
作者：
Jain AK;Allton K;Iacovino M;Mahen E;Milczarek RJ;Zwaka TP;Kyba M;Barton MC
通讯作者：
Barton MC
影响因子：
3.6
作者：
Fosbrink, Matthew;Cudrici, Cornelia;Tegla, Cosmin A.;Soloviova, Kateryna;Ito, Takahiro;Vlaicu, Sonia;Rus, Violeta;Niculescu, Florin;Rus, Horea
通讯作者：
Rus, Horea
影响因子：
6.1
作者：
Espinosa, Mario;Ortega, Rosa;Aljama, Pedro
通讯作者：
Aljama, Pedro