Activating transcription factor 3 (ATF3) promotes sublytic C5b-9-induced glomerular mesangial cells apoptosis through up-regulation of Gadd45α and KLF6 gene expression
Activating transcription factor 3 (ATF3) promotes sublytic C5b-9-induced glomerular mesangial cells apoptosis through up-regulation of Gadd45α and KLF6 gene expression
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激活转录因子 3 (ATF3) 通过上调 Gadd45α 和 KLF6 基因表达促进亚裂解 C5b-9 诱导的肾小球系膜细胞凋亡。
DOI：
10.1016/j.imbio.2011.02.005
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发表时间：
2011-08-01
期刊：
影响因子：
2.8
通讯作者：
Wang, Yingwei
中科院分区：
文献类型：
--
作者：
Xu, Kuanfeng;Zhou, Ying;Wang, Yingwei
亚溶性C5b-9复合物可导致肾小球系膜细胞凋亡，参与大鼠Thy-1肾炎的发生和发展。激活转录因子3 （activated transcription factor 3, ATF3）是细胞应对多种应激信号的直接早期基因，我们前期研究发现ATF3可促进亚溶C5b-9攻击的gmc细胞凋亡。但ATF3促进亚溶性C5b-9攻击引发的gmc凋亡的机制尚未阐明。本研究数据显示，在亚溶C5b-9刺激的指示时间内，GMCs中ATF3、生长阻滞和DNA损伤-45 α (Gadd45 α)、kruppel样因子6 （KLF6）和增殖细胞核抗原（PCNA）的表达显著升高，ATF3的表达可通过上调Gadd45 α和KLF6而非上调PCNA而导致GMCs凋亡。此外，Gadd45 α被鉴定为受ATF3直接调控的下游靶基因，KLF6可能受ATF3间接调控。爱思唯尔有限公司版权所有版权所有。
The sublytic C5b-9 complexes can result in glomerular mesangial cells (GMCs) apoptosis, which involved in the initiation and development of rat Thy-1 nephritis. Activating transcription factor 3 (ATF3) is an immediate early gene for cells to cope with a variety of stress signals, and our previous study revealed that ATF3 could promote GMCs apoptosis attacked by sublytic C5b-9. But the mechanism of ATF3 promoting GMCs apoptosis triggered by sublytic C5b-9 attack has not been elucidated. In this study, the data showed that the expression of ATF3, growth arrest and DNA damage-45 alpha (Gadd45 alpha.), Kruppel-like factor 6 (KLF6) and proliferating cell nuclear antigen (PCNA) in the GMCs in response to sublytic C5b-9 stimulation for the indicated time was significantly increased, and ATF3 expression could lead to GMCs apoptosis through up-regulation of Gadd45 alpha and KLF6, but not up-regulation of PCNA. Furthermore, Gadd45 alpha was identified as a downstream target gene regulated by ATF3 directly, and KLF6 might be regulated by ATF3 in an indirect manner. Crown Copyright (C) 2011 Published by Elsevier GmbH. All rights reserved.