Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-β Type II receptor
Journal of Biological Chemistry
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.
Du, B., Fu, C., Kent, K., Bush, H., Schulick, A., Kreiger, K., Collins, T., & McCaffrey, T. (2000). Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-β Type II receptor. Journal of Biological Chemistry, 275 (50). http://dx.doi.org/10.1074/jbc.M005159200