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.
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Acknowledgements
This work was supported by grants from the USPHS (HL63967, HL55397 and HL59488), the LeDucq Foundation and the Surgical Research Foundation.
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Yan, SF., Fujita, T., Lu, J. et al. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. Nat Med 6, 1355–1361 (2000). https://doi.org/10.1038/82168
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DOI: https://doi.org/10.1038/82168
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