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

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