Fu Mingui, Zhu Xiaojun, Zhang Jifeng, Liang Jian, Lin Yiming, Zhao Luning, Ehrengruber Markus U, Chen Yuqing E
Department of Biochemistry, Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, MEB 1345, Research Wing, Room 215, Atlanta, GA 30310, USA.
Gene. 2003 Oct 2;315:33-41. doi: 10.1016/s0378-1119(03)00730-3.
Early growth response factor 1 (Egr-1) is a key transcriptional factor to mediate gene expression after vascular injury. To better understand the role of Egr-1 in vasculature, we globally profiled Egr-1 target genes in human endothelial cells using adenoviral gene transfer and Affymetrix oligonucleotide-based microarray technology. More than 300 genes regulated by >/=3-fold with Egr-1 overexpression were identified and, partially, confirmed by Northern and Western blotting, including genes for transcriptional regulators, signaling proteins, cell cycle regulatory proteins, growth factors, and cytokines. Among them, thymus-expressed chemokine (TECK) and IP-30 were dramatically induced by Egr-1, but TNFalpha-related apoptosis inducing ligand (TRAIL) was significantly repressed by Egr-1, suggesting that Egr-1 is a key mediator of inflammation and apoptosis in vascular cells. These data provide novel Egr-1 target genes and contribute to the understanding of the role of Egr-1 in vasculature.
早期生长反应因子1(Egr-1)是介导血管损伤后基因表达的关键转录因子。为了更好地理解Egr-1在脉管系统中的作用,我们利用腺病毒基因转移和基于Affymetrix寡核苷酸的微阵列技术,对人内皮细胞中的Egr-1靶基因进行了全面分析。我们鉴定出300多个在Egr-1过表达时上调≥3倍的基因,并通过Northern和Western印迹法部分证实了这些基因,其中包括转录调节因子、信号蛋白、细胞周期调节蛋白、生长因子和细胞因子的相关基因。其中,胸腺表达趋化因子(TECK)和IP-30被Egr-1显著诱导,但肿瘤坏死因子α相关凋亡诱导配体(TRAIL)被Egr-1显著抑制,这表明Egr-1是血管细胞炎症和凋亡的关键介质。这些数据提供了新的Egr-1靶基因,有助于理解Egr-1在脉管系统中的作用。