FGF-1-induced platelet-derived growth factor-A chain gene expression in endothelial cells involves transcriptional activation by early growth response factor-1.

Abstract:

:Fibroblast growth factor-1 (FGF-1), a prototype member of the heparin-binding growth factor family, is a potent mitogen for vascular endothelial cells and a variety of other cell types. FGF-1 can induce the expression of the platelet-derived growth factor-A chain (PDGF-A) gene in endothelial cells; however, the underlying transcriptional mechanisms are not known. We used serial 5' deletion and transient transfection analysis of the human PDGF-A promoter to demonstrate that a 16-bp element, located 55 to 71 bp upstream of the transcriptional start site, is required for FGF-1-inducible promoter-dependent expression. This region contains nucleotide recognition elements for the early growth response gene product, early growth response factor-1 (Egr-1), and the related zinc-finger transcription factor, Sp1. Reverse-transcription polymerase chain reaction revealed that FGF-1 induced Egr-1 mRNA expression within 30 minutes. Electrophoretic mobility shift, supershift, and Western blot analysis demonstrated that Egr-1 protein accumulated in the nuclei of endothelial cells exposed to the growth factor, whereas levels of Sp1 did not change. Egr-1 bound to the FGF-1 response element in the proximal PDGF-A promoter in a specific and time-dependent manner. These findings indicate that Egr-1 plays a key regulatory role in FGF-1-inducible endothelial PDGF-A expression and implicate this transcription factor in pathological settings in which these mitogens are both expressed.

journal_name

Circ Res

journal_title

Circulation research

authors

Delbridge GJ,Khachigian LM

doi

10.1161/01.res.81.2.282

subject

Has Abstract

pub_date

1997-08-01 00:00:00

pages

282-8

issue

2

eissn

0009-7330

issn

1524-4571

journal_volume

81

pub_type

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