DOI: 10.1161/01.res.81.2.282. FGF-1–Induced Platelet-Derived Growth Factor-A Chain Gene Expression in Endothelial Cells Involves Transcriptional Activation by Early Growth Response Factor-1

FGF-1–Induced Platelet-Derived Growth Factor-A Chain Gene Expression in Endothelial Cells Involves Transcriptional Activation by Early Growth Response Factor-1

10.1161/01.res.81.2.282

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation Research (276)

Abstract

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.

Bibliography

Delbridge, G. J., & Khachigian, L. M. (1997). FGF-1âInduced Platelet-Derived Growth Factor-A Chain Gene Expression in Endothelial Cells Involves Transcriptional Activation by Early Growth Response Factor-1. Circulation Research, 81(2), 282â288.

Authors 2

Gabrielle J. Delbridge (first)
Levon M. Khachigian (additional)

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Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:47 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 4:45 p.m.)
Indexed	1 year ago (Aug. 26, 2024, 3:48 a.m.)
Issued	28 years ago (Aug. 1, 1997)
Published	28 years ago (Aug. 1, 1997)
Published Print	28 years ago (Aug. 1, 1997)

Funders 0

None

BibTeX

@article{Delbridge_1997, title={FGF-1–Induced Platelet-Derived Growth Factor-A Chain Gene Expression in Endothelial Cells Involves Transcriptional Activation by Early Growth Response Factor-1}, volume={81}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.81.2.282}, DOI={10.1161/01.res.81.2.282}, number={2}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Delbridge, Gabrielle J. and Khachigian, Levon M.}, year={1997}, month=aug, pages={282–288} }

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