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

Shi Fang Yan, Tomoyuki Fujita, Jiesheng Lu, Kenji Okada, Yu Shan Zou, Nigel Mackman, David J. Pinsky, David Stern

Research output: Contribution to journalArticle

350 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1355-1361
Number of pages7
JournalNature Medicine
Volume6
Issue number12
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

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Up-Regulation
Genes
Chemical activation
Switches
Ischemia
Growth
Reperfusion
Early Growth Response Protein 1
Animal Structures
Gene encoding
Chemokine Receptors
Vascular System Injuries
Zinc Fingers
Gene Deletion
Coagulation
Chemokines
Blood Vessels
Zinc
Permeability
Animals

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. / Yan, Shi Fang; Fujita, Tomoyuki; Lu, Jiesheng; Okada, Kenji; Shan Zou, Yu; Mackman, Nigel; Pinsky, David J.; Stern, David.

In: Nature Medicine, Vol. 6, No. 12, 01.12.2000, p. 1355-1361.

Research output: Contribution to journalArticle

Yan, SF, Fujita, T, Lu, J, Okada, K, Shan Zou, Y, Mackman, N, Pinsky, DJ & Stern, D 2000, 'Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress', Nature Medicine, vol. 6, no. 12, pp. 1355-1361. https://doi.org/10.1038/82168
Yan, Shi Fang ; Fujita, Tomoyuki ; Lu, Jiesheng ; Okada, Kenji ; Shan Zou, Yu ; Mackman, Nigel ; Pinsky, David J. ; Stern, David. / Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. In: Nature Medicine. 2000 ; Vol. 6, No. 12. pp. 1355-1361.
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