Abstract
A number of pathophysiologically relevant genes, including platelet-derived growth factor B-chain (PDGF-B), are induced in the vasculature after acute mechanical injury. In rat aorta, the activated expression of these genes was preceded by a marked increase in the amount of the early-growth-response gene product Egr-1 at the endothelial wound edge. Egr-1 interacts with a novel element in the proximal PDGF-B promoter, as well as with consensus elements in the promoters of other genes induced by endothelial injury. This interaction is crucial for injury-induced PDGF-B promoter-dependent expression. Sp1, whose binding site in the PDGF-B promoter overlaps that of Egr-1, occupies this element in unstimulated cells and is displaced by increasing amounts of Egr-1. These findings implicate Egr-1 in the up-regulated expression of PDGF-B and other potent mediators in mechanically injured arterial endothelial cells.
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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Animals
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Aorta / injuries
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Aorta / metabolism
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Base Sequence
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Binding Sites
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Early Growth Response Protein 1
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Endothelium, Vascular / injuries
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Endothelium, Vascular / metabolism*
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Gene Expression Regulation*
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Genes, Reporter
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Humans
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Immediate-Early Proteins*
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Male
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Molecular Sequence Data
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Platelet-Derived Growth Factor / biosynthesis
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Platelet-Derived Growth Factor / genetics*
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Promoter Regions, Genetic*
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / metabolism
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Sp1 Transcription Factor / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Zinc Fingers*
Substances
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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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Egr1 protein, rat
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Immediate-Early Proteins
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Platelet-Derived Growth Factor
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Recombinant Proteins
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Sp1 Transcription Factor
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Transcription Factors
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Tetradecanoylphorbol Acetate