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Titolo:
Extinguishing Egr-1-dependent inflammatory and thrombotic cascades following lung transplantation
Autore:
Okada, M; Fujita, T; Sakaguchi, T; Olson, KE; Collins, T; Stern, DM; Yan, SF; Pinsky, DJ;
Indirizzi:
Columbia Univ Coll Phys & Surg, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Harvard Univ, Sch Med, Boston, MA USA Harvard Univ Boston MA USAHarvard Univ, Sch Med, Boston, MA USA
Titolo Testata:
FASEB JOURNAL
fascicolo: 12, volume: 15, anno: 2001,
pagine: NIL_155 - NIL_172
SICI:
0892-6638(200110)15:12<NIL_155:EEIATC>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTERCELLULAR-ADHESION MOLECULE-1; PRIMARY GRAFT FAILURE; GENE-EXPRESSION; FIBRIN DEPOSITION; COMPARATIVE INHIBITION; OXYGEN DEPRIVATION; HYPOXIA; PRESERVATION; INJURY; TRANSCRIPTION;
Keywords:
early growth response-1; antisense oligodeoxyribonucleotide; transcription factor; ischemia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Pinsky, DJ Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA Columbia Univ Coll Phys & Surg 630 W 168th St New York NY USA 10032
Citazione:
M. Okada et al., "Extinguishing Egr-1-dependent inflammatory and thrombotic cascades following lung transplantation", FASEB J, 15(12), 2001, pp. NIL_155-NIL_172

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-1, tissue factor, and plasminogen activator inhibitor-1. The devastating functional consequences ofEgr-1 up-regulation in this setting are prevented by treating donor lungs with a phosphorothioate antisense oligodeoxyribonucleotide directed againstthe 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 12:41:57