Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China.
Cell Mol Immunol. 2010 Mar;7(2):143-51. doi: 10.1038/cmi.2009.109. Epub 2010 Feb 8.
Sublytic complement C5b-9 complexes can cause cell apoptosis, but the mechanism of glomerular mesangial cell (GMC) apoptosis mediated by these complexes has not been well defined. The activating transcription factor 3 (ATF3) gene is an immediate early gene for the cell to cope with a variety of stress signals and can promote apoptosis of some cells. In this study, ATF3 expression and cell apoptosis in GMCs induced by sublytic C5b-9 were measured, and then the effects of ATF3 gene over-expression or knockdown on GMC apoptosis induced by sublytic C5b-9 were examined at a fixed time. The results showed that both ATF3 expression and GMC apoptosis were markedly increased and ATF3 over-expression obviously increased sublytic C5b-9-induced GMC apoptosis, whereas ATF3 gene silencing had a significant opposite effect. Collectively, these findings indicate that upregulation of ATF3 gene expression is involved in regulating GMC apoptosis induced by sublytic C5b-9 complexes.
亚溶血性 C5b-9 复合物可引起细胞凋亡，但这些复合物介导的肾小球系膜细胞（GMC）凋亡的机制尚未完全明确。激活转录因子 3（ATF3）基因是细胞应对各种应激信号的即刻早期基因，可促进某些细胞的凋亡。在这项研究中，测量了亚溶血性 C5b-9 诱导的 GMC 中 ATF3 的表达和细胞凋亡，然后在固定时间检查 ATF3 基因过表达或敲低对亚溶血性 C5b-9 诱导的 GMC 凋亡的影响。结果表明，ATF3 的表达和 GMC 的凋亡均明显增加，ATF3 的过表达明显增加了亚溶血性 C5b-9 诱导的 GMC 凋亡，而 ATF3 基因沉默则有明显的相反作用。综上所述，这些发现表明，ATF3 基因表达的上调参与调节亚溶血性 C5b-9 复合物诱导的 GMC 凋亡。
