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

Nat Med. 2000 Dec;6(12):1355-61. doi: 10.1038/82168.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Coagulation Factors / biosynthesis
  • Chemokines / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Early Growth Response Protein 1
  • Endothelial Growth Factors / biosynthesis
  • Genes, Switch
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Lipopolysaccharides / toxicity
  • Lung / blood supply
  • Lung / pathology*
  • Lymphokines / biosynthesis
  • Mice
  • Mice, Mutant Strains
  • Reperfusion Injury / etiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Up-Regulation
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Zinc Fingers / genetics


  • Blood Coagulation Factors
  • Chemokines
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Endothelial Growth Factors
  • Immediate-Early Proteins
  • Lipopolysaccharides
  • Lymphokines
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Intercellular Adhesion Molecule-1