Key result
Mechanical injury or PMA induces PDGF A-chain transcription in smooth muscle cells via Egr-1 displacement.
This study identifies the molecular mechanism by which Egr-1 displaces Sp1 and Sp3 to induce PDGF A-chain transcription in vascular smooth muscle cells following injury.
Does not inform clinical practice; leaves open Egr-1 as a therapeutic target in human vascular disease.
Platelet-derived growth factor (PDGF) A-chain is expressed by vascular smooth muscle cells (SMC) in a variety of pathological settings. Phorbol 12-myristate 13-acetate (PMA) increases A-chain transcription and was used as a model agonist. Transient transfection analysis identified a region in the promoter that is required for inducibility, located between base pairs -71 and -55 from the transcription start site. This region contains overlapping recognition elements for members of the Sp and Egr families. Egr-1 transcript and protein increased after PMA treatment, whereas Sp1 and Sp3 levels remain unchanged. Egr-1 expression and PDGF A-chain promoter activity also increased in cells exposed to PDGF or mechanical injury. In vitro binding assays demonstrated that Egr-1, Sp1, and Sp3 can bind to this promoter region and that increasing Egr-1 can displace both Sp1 and Sp3. In an in vivo model of arterial injury, Egr-1 expression was induced concurrently with the expression of PDGF-A in SMC. Displacement of Sp1 and Sp3 by Egr-1 is correlated with inducible PDGF A-chain expression in the vessel wall.
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Silverman et al. (1997) studied this question. Phorbol 12-myristate 13-acetate (PMA), PDGF, or mechanical injury was evaluated on PDGF A-chain transcription and promoter activity. Egr-1 displacement of Sp1 and Sp3 mediates inducible PDGF A-chain transcription in smooth muscle cells following exposure to PMA, PDGF, or mechanical injury.
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