| First Author | Zhang J | Year | 2023 |
| Journal | J Immunol | Volume | 211 |
| Issue | 12 | Pages | 1835-1843 |
| PubMed ID | 37930129 | Mgi Jnum | J:343584 |
| Mgi Id | MGI:7568966 | Doi | 10.4049/jimmunol.2300043 |
| Citation | Zhang J, et al. (2023) Oxidative Stress Induces E-Selectin Expression through Repression of Endothelial Transcription Factor ERG. J Immunol 211(12):1835-1843 |
| abstractText | Oxidative stress induces a prothrombotic state through enhancement of adhesion properties of the endothelium. E-selectin, an endothelial cell adhesion molecule, becomes a therapeutic target for venous thrombosis, whereas the regulatory mechanisms of its expression have not been fully understood. In the present study, we report that H2O2 treatment increases expression of E-selectin but decreases expression of the endothelial transcription factor ETS-related gene (ERG) in HUVECs in a dose- and time-dependent manner. In BALB/c mice treated with hypochlorous acid, E-selectin expression is increased and ERG expression is decreased in endothelial cells of the brain and lung. RNA interference of ERG upregulates E-selectin expression, whereas transfection of ERG-expressing plasmid downregulates E-selectin expression in HUVECs. Knockdown or overexpression of ERG comprises H2O2-induced E-selectin expression in HUVECs. Deletion of the Erg gene in mice results in embryonic lethality at embryonic days 10.5-12.5, and E-selectin expression is increased in the Erg-/- embryos. No chromatin loop was found on the E-selectin gene or its promoter region by capture high-throughput chromosome conformation capture. Chromatin immunoprecipitation and luciferase reporter assay determined that the -127 ERG binding motif mediates ERG-repressed E-selectin promoter activity. In addition, ERG decreases H2O2-induced monocyte adhesion. Together, ERG represses the E-selectin gene transcription and inhibits oxidative stress-induced endothelial cell adhesion. |
