Egr-1-Induced Endothelial Gene Expression: A Common Theme in Vascular Injury

• Published in: Science (American Association for the Advancement of Science) Vol. 271; no. 5254; pp. 1427 - 1431
• Main Authors: Khachigian, Levon M., Lindner, Volkhard, Williams, Amy J., Collins, Tucker
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 08-03-1996; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Aorta; Aorta - injuries; Aorta - metabolism; Base Sequence; Binding Sites; Biological and medical sciences; Blood vessels; Cellular biology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Early Growth Response Protein 1; Endothelial cells; Endothelium; Endothelium, Vascular - injuries; Endothelium, Vascular - metabolism; Fundamental and applied biological sciences. Psychology; Gels; Gene expression; Gene Expression Regulation; Genes; Genes, Reporter; Humans; Immediate-Early Proteins; Injuries; Logical Thinking; Male; Messenger RNA; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Physical trauma; Platelet-Derived Growth Factor - biosynthesis; Platelet-Derived Growth Factor - genetics; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; Recombinant Proteins - metabolism; Sp1 Transcription Factor - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing; Transcripts (Written Records); Vascular endothelium; Vascular system injuries; Wounds; Zinc Fingers; Rat; Transcription promoter; Injury; Rodentia; Molecular interaction; Gene expression; Artery; Endothelium; Cell motility; Vertebrata; Regulation(control); Mammalia; Gene; Blood vessel; Vascular wall; Platelet derived growth factor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.271.5254.1427

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.