Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-β Type II receptor
Authors / Editors
Research Areas
No matching items found.
Publication Details
Output type: Journal article
Author list: Du B., Fu C., Kent K., Bush H., Schulick A., Kreiger K., Collins T., McCaffrey T.
Publisher: Elsevier
Publication year: 2000
Journal: Journal of Biological Chemistry (0021-9258)
Volume number: 275
Issue number: 50
Start page: 39039
End page: 39047
Number of pages: 9
ISSN: 0021-9258
eISSN: 1083-351X
URL: http://api.elsevier.com/content/abstract/scopus_id:0034671736
Unpaywall Data
Open access status: hybrid
Full text URL: http://www.jbc.org/content/275/50/39039.full.pdf
Abstract
Atherosclerotic lesions may progress due to a "failure to die" by vascular repair cells. Egr-1, a zinc finger transcription factor, is elevated more than 5-fold in human carotid lesions relative to the adjacent tunica media. Lesion cells in vitro also express 2-3-fold higher Egr-1 mRNA and protein levels but express much lower levels of the transforming growth factor-β (TGF-β) Type II receptor (TβR-2) and are functionally resistant to the antiproliferative effects of TGF-β. Lesion cells fail to express a TβR-2 promoter/chloramphenicol acetyltransferase (CAT) construct but overexpress an Egr-1-inducible platelet-derived growth factor-A promoter/CAT construct. Transfection of Egr-1 cDNA represses TβR-2/CAT constructs but induces PDGF-A/CAT. Egr-1 transfection reduces the levels of TβR-2 and confers resistance to the antiproliferative effect of TGF-β1. Egr-1 can interact directly with both the -143 Sp1 site and the positive regulatory element 2 (PRE2) (ERT/ets) region of the TβR-2 promoter. Thus, although activating a family of stress-responsive genes, Egr-1 also transcriptionally represses one of the major inhibitory pathways that restrains vascular repair.
Keywords
No matching items found.
Documents
No matching items found.
