1. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress.
- Author
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Yan, Shi-Fang, Fujita, Tomoyuki, Lu, Jiesheng, Okada, Kenji, Shan Zou, Yu, Mackman, Nigel, Pinsky, David J., and Stern, David M.
- Subjects
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ISCHEMIA , *TRANSCRIPTION factors , *GENETICS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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