RGD Reference Report - Early growth response gene-1 promotes airway allograft rejection. - Rat Genome Database

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Early growth response gene-1 promotes airway allograft rejection.

Authors: Harada, H  Lama, VN  Badri, LN  Ohtsuka, T  Petrovic-Djergovic, D  Liao, H  Yoshikawa, Y  Iwanaga, K  Lau, CL  Pinsky, DJ 
Citation: Harada H, etal., Am J Physiol Lung Cell Mol Physiol. 2007 Jul;293(1):L124-30. Epub 2007 Mar 23.
RGD ID: 5132266
Pubmed: PMID:17384085   (View Abstract at PubMed)
DOI: DOI:10.1152/ajplung.00285.2006   (Journal Full-text)

Chronic airway rejection, characterized by lymphocytic bronchitis, epithelial cell damage, and obliterative bronchiolitis (OB), limits long-term survival after lung transplantation. The transcription factor early growth response gene-1 (Egr-1) induces diverse inflammatory mediators, some involved in OB pathogenesis. An orthotopic mouse tracheal transplant model was used to determine whether Egr-1 promotes development of airway allograft rejection. Significantly higher Egr-1 mRNA levels were seen in allografts (3.2-fold increase vs. isografts, P = 0.012). Allografts revealed thickening of epithelial and subepithelial airway layers (51 +/- 4% luminal encroachment for allografts vs. 20 +/- 3% for isografts, P < 0.0001) marked by significant lymphocytic infiltration. Absence of the Egr-1 gene in donor (but not recipient) tissue resulted in significant reduction in luminal narrowing (34 +/- 4%, P = 0.0001) with corresponding diminution of T cell infiltration. Egr-1 null allografts exhibited a striking reduction in inducible nitric oxide synthase (iNOS) expression. Effector cytokines previously implicated in OB pathogenesis with known Egr-1 promoter motifs (IL-1beta and JE/monocyte chemoattractant protein-1) were reduced in Egr-1 null allografts. These data suggest a paradigm wherein local induction of Egr-1 in tracheal allografts drives expression of inflammatory mediators responsible for lymphocyte recruitment and tissue destruction characteristic of airway rejection.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EGR1Humanbronchitis  ISOEgr1 (Mus musculus) RGD 
Egr1Ratbronchitis  ISOEgr1 (Mus musculus) RGD 
Egr1Mousebronchitis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egr1  (early growth response 1)

Genes (Mus musculus)
Egr1  (early growth response 1)

Genes (Homo sapiens)
EGR1  (early growth response 1)


Additional Information