Inducible PDGF A-chain transcription in smooth muscle cells is mediated by Egr-1 displacement of Sp1 and Sp3.

Publication/Presentation Date

9-1-1997

Abstract

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.

Volume

273

Issue

3 Pt 2

First Page

1415

Last Page

1426

ISSN

0002-9513

Disciplines

Medicine and Health Sciences

PubMedID

9321833

Department(s)

Department of Medicine

Document Type

Article

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