Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress

Abstract

Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion receptor, procoagulant and permeability-related genes are coordinately upregulated by rapid ischemia-mediated activation of Egr-1. Deletion of the gene encoding Egr-1 strikingly diminished expression of these mediators of vascular injury in a murine model of lung ischemia/reperfusion, and enhanced animal survival and organ function. Rapid activation of Egr-1 in response to oxygen deprivation primes the vasculature for dysfunction manifest during reperfusion. These studies define a central and unifying role for Egr-1 activation in the pathogenesis of ischemic tissue damage.

A New Role for Downstream Toll-like Receptor Signaling in Mediating Immediate Early Gene Expression during Focal Cerebral Ischemia

“…n ¼ 3 per time point and N ¼ 9 per WT, MyD, and TRIF for all analyses. a number of downstream genes such as, MMP-9, 21 E-Selectin, 23 ICAM-1, [16][17][18][19] and VCAM-1, 20 important in mediating immune responses to focal cerebral ischemia.…”

“…of MyD88 Compared to Wild-Type Mice following Focal Cerebral Ischemia To determine whether the abnormal immediate early gene expression observed in mice with deficiencies of MyD88 or TRIF had any effect on expression of downstream genes involved in different aspects of immune activation such as ICAM-1, [16][17][18][19] E-Selectin, VCAM-1, 20 MMP-9, 21 and tPAI-1, 16,22 we analyzed protein levels of these genes at baseline, and following pMCAO.…”

Requirement of phospholipase C‐γ2 (PLCγ2) for Dectin‐1‐induced antigen presentation and induction of TH1/TH17 polarization

“…Egr1 is an AP-1-dependent transcription factor that coordinates the expression of various proinflammatory genes, including TNF-a and IL-6 [34,41,42]. Moreover, Egr1 can also bind the human IL-2 promoter [32].…”

Introduction of DNA enzyme for Egr-1 into tubulointerstitial fibroblasts by electroporation reduced interstitial α-smooth muscle actin expression and fibrosis in unilateral ureteral obstruction (UUO) rats

“…Recently, activation of Egr-1 was shown to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. 32 Deletion of the gene encoding Egr-1 strikingly diminished expression of these mediators of vascular injury in a murine model of lung ischemia/reperfusion injury, and enhanced animal survival and organ function. We found the elevated Egr-1 expression immediately after ureteral obstruction before the expression of a set of fibrogenic genes.…”