Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation.

M. Okada, T. Fujita, T. Sakaguchi, K. E. Olson, T. Collins, David Stern, S. F. Yan, D. J. Pinsky

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Hypoxic induction of the early growth response-1 (Egr-1) transcription factor initiates proinflammatory and procoagulant gene expression. Orthotopic/isogeneic rat lung transplantation triggers Egr-1 expression and nuclear DNA binding activity corresponding to Egr-1, which leads to increased expression of downstream target genes such as interleukin-1b, tissue factor, and plasminogen activator inhibitor-1. The devastating functional consequences of Egr-1 up-regulation in this setting are prevented by treating donor lungs with a phosphorothioate antisense oligodeoxyribonucleotide directed against the Egr-1 translation initiation site, which blocks expression of Egr-1 and its gene targets. Post-transplant graft leukostasis, inflammation, and thrombosis are consequently diminished, with marked improvement in graft function and recipient survival. Blocking expression of a proximal transcription factor, which activates deleterious inflammatory and coagulant effector mechanisms, is an effective molecular strategy to improve organ preservation.

Original languageEnglish (US)
Pages (from-to)2757-2759
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume15
Issue number14
StatePublished - Jan 1 2001

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Lung Transplantation
Growth
Transplants
Grafts
Antisense Oligodeoxyribonucleotides
Early Growth Response Protein 1
Leukostasis
Genes
Organ Preservation
Coagulants
Interleukins
Plasminogen Activator Inhibitor 1
Thromboplastin
Tissue Plasminogen Activator
Gene expression
Rats
Thrombosis
Transcription Factors
Up-Regulation
Inflammation

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation. / Okada, M.; Fujita, T.; Sakaguchi, T.; Olson, K. E.; Collins, T.; Stern, David; Yan, S. F.; Pinsky, D. J.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 15, No. 14, 01.01.2001, p. 2757-2759.

Research output: Contribution to journalArticle

Okada, M. ; Fujita, T. ; Sakaguchi, T. ; Olson, K. E. ; Collins, T. ; Stern, David ; Yan, S. F. ; Pinsky, D. J. / Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2001 ; Vol. 15, No. 14. pp. 2757-2759.
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