Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation.
FASEB J
; 15(14): 2757-9, 2001 Dec.
Article
de En
| MEDLINE
| ID: mdl-11606484
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.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Thrombose
/
Facteurs de transcription
/
Transplantation pulmonaire
/
Protéines précoces immédiates
/
Protéines de liaison à l'ADN
/
Inflammation
Limites:
Animals
Langue:
En
Journal:
FASEB J
Sujet du journal:
BIOLOGIA
/
FISIOLOGIA
Année:
2001
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique