Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Apoptosis Regulatory Proteins
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Blotting, Northern
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Blotting, Western
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Cell Line
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Cell Line, Tumor
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Chemokines, CC / genetics
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Chemokines, CC / metabolism
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / physiology
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Down-Regulation
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Early Growth Response Protein 1
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Endothelium, Vascular / cytology
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Endothelium, Vascular / metabolism*
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Gene Expression Profiling
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Gene Expression Regulation
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Genetic Vectors / genetics
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Humans
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Immediate-Early Proteins*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Oligonucleotide Array Sequence Analysis / methods
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Oxidoreductases Acting on Sulfur Group Donors
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Oxidoreductases*
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Proteins / genetics
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Proteins / metabolism
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TNF-Related Apoptosis-Inducing Ligand
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Transcription Factors / genetics*
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Transcription Factors / physiology
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Transfection
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Apoptosis Regulatory Proteins
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CCL25 protein, human
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Chemokines, CC
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DNA-Binding Proteins
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EGR1 protein, human
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Early Growth Response Protein 1
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Immediate-Early Proteins
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Membrane Glycoproteins
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Proteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Transcription Factors
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Tumor Necrosis Factor-alpha
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Oxidoreductases
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IFI30 protein, human
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Oxidoreductases Acting on Sulfur Group Donors