Department of Microbiology and Immunology, Nanjing Medical University, 140 Nanjing Hanzhong Road, Nanjing, PR China.
Immunobiology. 2011 Aug;216(8):871-81. doi: 10.1016/j.imbio.2011.02.005. Epub 2011 Feb 22.
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 (Gadd45α), Krüppel-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 Gadd45α and KLF6, but not up-regulation of PCNA. Furthermore, Gadd45α was identified as a downstream target gene regulated by ATF3 directly, and KLF6 might be regulated by ATF3 in an indirect manner.
亚毒性 C5b-9 复合物可导致肾小球系膜细胞 (GMC) 凋亡，这涉及到大鼠 Thy-1 肾炎的起始和发展。激活转录因子 3 (ATF3) 是细胞应对各种应激信号的即刻早期基因，我们之前的研究表明 ATF3 可以促进亚毒性 C5b-9 攻击引发的 GMC 凋亡。但是，ATF3 促进亚毒性 C5b-9 攻击引发的 GMC 凋亡的机制尚未阐明。在这项研究中，数据表明，在亚毒性 C5b-9 刺激下，GMC 中 ATF3、生长停滞和 DNA 损伤 45 阿尔法 (Gadd45α)、Krüppel 样因子 6 (KLF6) 和增殖细胞核抗原 (PCNA) 的表达随时间的推移显著增加，并且 ATF3 的表达可以通过上调 Gadd45α 和 KLF6 导致 GMC 凋亡，而不是上调 PCNA。此外，Gadd45α 被鉴定为 ATF3 直接调控的下游靶基因，而 KLF6 可能通过间接方式受 ATF3 调控。
