[en] As asthma physiopathology is complex and not fully understood to date; it is expected that new key mediators are still to be unveiled in this disease. The main objective of this study was to discover potential new target proteins with a molecular weight >20 kDa by using two-dimensional differential in-gel electrophoresis (2D-DIGE) on lung parenchyma extracts from control or allergen-exposed mice (ovalbumin). Two different mouse models leading to the development of acute airway inflammation (5 days allergen exposure) and airway remodeling (10 weeks allergen exposure) were used. This experimental setting allowed the discrimination of 33 protein spots in the acute inflammation model and 31 spots in the remodeling model displaying a differential expression. Several proteins were then identified by MALDI-TOF/TOF MS. Among those differentially expressed proteins, PDIA6, GRP78, Annexin A6, hnRPA3, and Enolase display an increased expression in lung parenchyma from mice exposed to allergen for 5 days. Conversely, Apolipoprotein A1 was shown to be decreased after allergen exposure in the same model. Analysis on lung parenchyma of mice exposed to allergens for 10 weeks showed decreased calreticulin levels. Changes in the levels of those different mediators were confirmed by Western blot and immunohistochemical analysis. Interestingly, alveolar macrophages isolated from lungs in the acute inflammation model displayed enhanced levels of GRP78. Moreover, intratracheal instillation of anti-GRP78 siRNA in allergen-exposed animals led to a decrease in eosinophilic inflammation and bronchial hyperresponsiveness. This study unveils new mediators of potential importance that are up- and down-regulated in asthma. Among up-regulated mediators, GRP-78 appears as a potential new therapeutic target worthy of further investigations.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Quesada Calvo, Florence ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Fillet, Marianne ✱; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Renaut, Jenny
Crahay, Céline
Guéders, Maud ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.
Hacha, Jonathan ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Paulissen, Geneviève ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Rocks, Natacha ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Leprince, Pierre ; Université de Liège - ULiège > GIGA - Neurosciences
Cataldo, Didier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.
✱ These authors have contributed equally to this work.
Language :
English
Title :
Potential Therapeutic Target Discovery by 2D-DIGE Proteomic Analysis in Mouse Models of Asthma
Publication date :
2011
Journal title :
Journal of Proteome Research
ISSN :
1535-3893
eISSN :
1535-3907
Publisher :
American Chemical Society, Washington, United States - District of Columbia
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