[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
Dekkers, B. G.; Maarsingh, H.; Meurs, H.; Gosens, R. Airway structural components drive airway smooth muscle remodeling in asthma Proc. Am. Thorac. Soc. 2009, 6 (8) 683-92
Gueders, M. M.; Bertholet, P.; Perin, F.; Rocks, N.; Maree, R.; Botta, V.; Louis, R.; Foidart, J. M.; Noel, A.; Evrard, B.; Cataldo, D. D. A novel formulation of inhaled doxycycline reduces allergen-induced inflammation, hyperresponsiveness and remodeling by matrix metalloproteinases and cytokines modulation in a mouse model of asthma Biochem. Pharmacol. 2008, 75 (2) 514-26 (Pubitemid 350298479)
Bourdin, A.; Neveu, D.; Vachier, I.; Paganin, F.; Godard, P.; Chanez, P. Specificity of basement membrane thickening in severe asthma J. Allergy Clin. Immunol. 2007, 119 (6) 1367-74 (Pubitemid 46855858)
Broide, D. H. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling J. Allergy Clin. Immunol 2008, 121 (3) 560-70; quiz 571-2 (Pubitemid 351323873)
Cataldo, D. D.; Tournoy, K. G.; Vermaelen, K.; Munaut, C.; Foidart, J. M.; Louis, R.; Noel, A.; Pauwels, R. A. Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation Am. J. Pathol. 2002, 161 (2) 491-8 (Pubitemid 36142158)
Di Valentin, E.; Crahay, C.; Garbacki, N.; Hennuy, B.; Gueders, M.; Noel, A.; Foidart, J. M.; Grooten, J.; Colige, A.; Piette, J.; Cataldo, D. New asthma biomarkers: lessons from murine models of acute and chronic asthma Am. J. Physiol. Lung Cell Mol. Physiol. 2009, 296 (2) L185-97
Gueders, M. M.; Paulissen, G.; Crahay, C.; Quesada-Calvo, F.; Hacha, J.; Van Hove, C.; Tournoy, K.; Louis, R.; Foidart, J. M.; Noel, A.; Cataldo, D. D. Mouse models of asthma: a comparison between C57BL/6 and BALB/c strains regarding bronchial responsiveness, inflammation, and cytokine production Inflamm. Res. 2009, 58 (12) 845-54
Van Hove, C. L.; Maes, T.; Cataldo, D. D.; Gueders, M. M.; Palmans, E.; Joos, G. F.; Tournoy, K. G. Comparison of acute inflammatory and chronic structural asthma-like responses between C57BL/6 and BALB/c mice Int. Arch. Allergy Immunol. 2009, 149 (3) 195-207
Calvo, F. Q.; Fillet, M.; de Seny, D.; Meuwis, M. A.; Maree, R.; Crahay, C.; Paulissen, G.; Rocks, N.; Gueders, M.; Wehenkel, L.; Merville, M. P.; Louis, R.; Foidart, J. M.; Noel, A.; Cataldo, D. Biomarker discovery in asthma-related inflammation and remodeling Proteomics 2009, 9 (8) 2163-70
Jamesdaniel, S.; Salvi, R.; Coling, D. Auditory proteomics: methods, accomplishments and challenges Brain Res. 2009, 1277, 24-36
Maes, T.; Provoost, S.; Lanckacker, E. A.; Cataldo, D. D.; Vanoirbeek, J. A.; Nemery, B.; Tournoy, K. G.; Joos, G. F. Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation Respir Res. 2010, 11, 7
Fajardo, I.; Svensson, L.; Bucht, A.; Pejler, G. Increased levels of hypoxia-sensitive proteins in allergic airway inflammation Am. J. Respir Crit. Care Med. 2004, 170 (5) 477-84 (Pubitemid 39209127)
Fehniger, T. E.; Sato-Folatre, J. G.; Malmstrom, J.; Berglund, M.; Lindberg, C.; Brange, C.; Lindberg, H.; Marko-Varga, G. Exploring the context of the lung proteome within the airway mucosa following allergen challenge J. Proteome Res. 2004, 3 (2) 307-20 (Pubitemid 38500999)
Jeong, H.; Rhim, T.; Ahn, M. H.; Yoon, P. O.; Kim, S. H.; Chung, I. Y.; Uh, S.; Kim, S. I.; Park, C. S. Proteomic analysis of differently expressed proteins in a mouse model for allergic asthma J. Korean Med. Sci. 2005, 20 (4) 579-85 (Pubitemid 41265134)
Haenen, S.; Vanoirbeek, J. A.; De Vooght, V.; Maes, E.; Schoofs, L.; Nemery, B.; Hoet, P. H.; Clynen, E. Proteome analysis of multiple compartments in a mouse model of chemical-induced asthma J. Proteome Res. 2010, 9 (11) 5868-76
Houtman, R.; Krijgsveld, J.; Kool, M.; Romijn, E. P.; Redegeld, F. A.; Nijkamp, F. P.; Heck, A. J.; Humphery-Smith, I. Lung proteome alterations in a mouse model for nonallergic asthma Proteomics 2003, 3 (10) 2008-18 (Pubitemid 37309352)
Wu, C. C.; Chien, K. Y.; Tsang, N. M.; Chang, K. P.; Hao, S. P.; Tsao, C. H.; Chang, Y. S.; Yu, J. S. Cancer cell-secreted proteomes as a basis for searching potential tumor markers: nasopharyngeal carcinoma as a model Proteomics 2005, 5 (12) 3173-82
Roh, G. S.; Shin, Y.; Seo, S. W.; Yoon, B. R.; Yeo, S.; Park, S. J.; Cho, J. W.; Kwack, K. Proteome analysis of differential protein expression in allergen-induced asthmatic mice lung after dexamethasone treatment Proteomics 2004, 4 (11) 3318-27 (Pubitemid 39525279)
Verrills, N. M.; Irwin, J. A.; Yan, He, X.; Wood, L. G.; Powell, H.; Simpson, J. L.; McDonald, V. M.; Sim, A.; Gibson, P. G. Identification of novel diagnostic biomarkers for asthma and chronic obstructive pulmonary disease Am. J. Respir. Crit. Care Med. 2011, 183 (12) 1633-43
Petrak, J.; Ivanek, R.; Toman, O.; Cmejla, R.; Cmejlova, J.; Vyoral, D.; Zivny, J.; Vulpe, C. D. Deja vu in proteomics. A hit parade of repeatedly identified differentially expressed proteins Proteomics 2008, 8 (9) 1744-9 (Pubitemid 351678270)
Hotamisligil, G. S. Endoplasmic reticulum stress and atherosclerosis Nat. Med. 2010, 16 (4) 396-9
Imai, Y.; Soda, M.; Inoue, H.; Hattori, N.; Mizuno, Y.; Takahashi, R. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin Cell 2001, 105 (7) 891-902 (Pubitemid 32635090)
Nakagawa, T.; Zhu, H.; Morishima, N.; Li, E.; Xu, J.; Yankner, B. A.; Yuan, J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta Nature 2000, 403 (6765) 98-103 (Pubitemid 30038529)
Lee, A. S. GRP78 induction in cancer: therapeutic and prognostic implications Cancer Res. 2007, 67 (8) 3496-9 (Pubitemid 46762126)
Li, J.; Lee, A. S. Stress induction of GRP78/BiP and its role in cancer Curr. Mol. Med. 2006, 6 (1) 45-54
Gonzalez-Gronow, M.; Selim, M. A.; Papalas, J.; Pizzo, S. V. GRP78: a multifunctional receptor on the cell surface Antioxid. Redox. Signal. 2009, 11 (9) 2299-306
Philippova, M.; Ivanov, D.; Joshi, M. B.; Kyriakakis, E.; Rupp, K.; Afonyushkin, T.; Bochkov, V.; Erne, P.; Resink, T. J. Identification of proteins associating with glycosylphosphatidylinositol- anchored T-cadherin on the surface of vascular endothelial cells: role for Grp78/BiP in T-cadherin-dependent cell survival Mol. Cell. Biol. 2008, 28 (12) 4004-17 (Pubitemid 351812986)
Zhang, L. H.; Zhang, X. Roles of GRP78 in physiology and cancer J. Cell Biochem. 2010, 110 (6) 1299-305
Quinones, Q. J.; de Ridder, G. G.; Pizzo, S. V. GRP78: a chaperone with diverse roles beyond the endoplasmic reticulum Histol. Histopathol. 2008, 23 (11) 1409-16
Misra, U. K.; Pizzo, S. V. Ligation of cell surface GRP78 with antibody directed against the COOH-terminal domain of GRP78 suppresses Ras/MAPK and PI 3-kinase/AKT signaling while promoting caspase activation in human prostate cancer cells Cancer Biol. Ther. 2010, 9 (2) 142-52
Murphy, D. M.; O'Byrne, P. M. Recent advances in the pathophysiology of asthma Chest 2010, 137 (6) 1417-26
Hardy, B.; Battler, A.; Weiss, C.; Kudasi, O.; Raiter, A. Therapeutic angiogenesis of mouse hind limb ischemia by novel peptide activating GRP78 receptor on endothelial cells Biochem. Pharmacol. 2008, 75 (4) 891-9 (Pubitemid 351174112)
Kern, J.; Untergasser, G.; Zenzmaier, C.; Sarg, B.; Gastl, G.; Gunsilius, E.; Steurer, M. GRP-78 secreted by tumor cells blocks the antiangiogenic activity of bortezomib Blood 2009, 114 (18) 3960-7
Rosati, E.; Sabatini, R.; Rampino, G.; De Falco, F.; Di Ianni, M.; Falzetti, F.; Fettucciari, K.; Bartoli, A.; Screpanti, I.; Marconi, P. Novel targets for endoplasmic reticulum stress-induced apoptosis in B-CLL. Blood 2010, not supplied.
Bani, D.; Giannini, L.; Ciampa, A.; Masini, E.; Suzuki, Y.; Menegazzi, M.; Nistri, S.; Suzuki, H. Epigallocatechin-3-gallate reduces allergen-induced asthma-like reaction in sensitized guinea pigs J. Pharmacol. Exp. Ther. 2006, 317 (3) 1002-11 (Pubitemid 43764102)
Luo, S.; Mao, C.; Lee, B.; Lee, A. S. GRP78/BiP is required for cell proliferation and protecting the inner cell mass from apoptosis during early mouse embryonic development Mol. Cell. Biol. 2006, 26 (15) 5688-97 (Pubitemid 44134326)
Turano, C.; Coppari, S.; Altieri, F.; Ferraro, A. Proteins of the PDI family: unpredicted non-ER locations and functions J. Cell Physiol. 2002, 193 (2) 154-63
Herbon, N.; Werner, M.; Braig, C.; Gohlke, H.; Dutsch, G.; Illig, T.; Altmuller, J.; Hampe, J.; Lantermann, A.; Schreiber, S.; Bonifacio, E.; Ziegler, A.; Schwab, S.; Wildenauer, D.; van den Boom, D.; Braun, A.; Knapp, M.; Reitmeir, P.; Wjst, M. High-resolution SNP scan of chromosome 6p21 in pooled samples from patients with complex diseases Genomics 2003, 81 (5) 510-8 (Pubitemid 36434226)
Hui, J.; Palmer, L. J.; James, A. L.; Musk, A. W.; Beilby, J. P. AluyMICB dimorphism within the class I region of the major histocompatibility complex is associated with asthma and airflow obstruction in the Busselton population Clin. Exp. Allergy 2006, 36 (6) 728-34 (Pubitemid 43977418)
Camors, E.; Monceau, V.; Charlemagne, D. Annexins and Ca 2+ handling in the heart Cardiovasc. Res. 2005, 65 (4) 793-802 (Pubitemid 40249725)
Bode, G.; Luken, A.; Kerkhoff, C.; Roth, J.; Ludwig, S.; Nacken, W. Interaction between S100A8/A9 and annexin A6 is involved in the calcium-induced cell surface exposition of S100A8/A9 J. Biol. Chem. 2008, 283 (46) 31776-84
Halayko, A. J.; Ghavami, S. S100A8/A9: a mediator of severe asthma pathogenesis and morbidity? Can. J. Physiol. Pharmacol. 2009, 87 (10) 743-55
Ma, A. S.; Moran-Jones, K.; Shan, J.; Munro, T. P.; Snee, M. J.; Hoek, K. S.; Smith, R. Heterogeneous nuclear ribonucleoprotein A3, a novel RNA trafficking response element-binding protein J. Biol. Chem. 2002, 277 (20) 18010-20 (Pubitemid 34967613)
Nahm, D. H.; Lee, K. H.; Shin, J. Y.; Ye, Y. M.; Kang, Y.; Park, H. S. Identification of alpha-enolase as an autoantigen associated with severe asthma J. Allergy Clin. Immunol. 2006, 118 (2) 376-81 (Pubitemid 44142703)
Nicholas, B. L.; Skipp, P.; Barton, S.; Singh, D.; Bagmane, D.; Mould, R.; Angco, G.; Ward, J.; Guha-Niyogi, B.; Wilson, S.; Howarth, P.; Davies, D. E.; Rennard, S.; O'Connor, C. D.; Djukanovic, R. Identification of lipocalin and apolipoprotein A1 as biomarkers of chronic obstructive pulmonary disease Am. J. Respir. Crit. Care Med. 2010, 181 (10) 1049-60
Li, Y.; Dong, J. B.; Wu, M. P. Human ApoA-I overexpression diminishes LPS-induced systemic inflammation and multiple organ damage in mice Eur. J. Pharmacol. 2008, 590 (1-3) 417-22
Nandedkar, S. D.; Weihrauch, D.; Xu, H.; Shi, Y.; Feroah, T.; Hutchins, W.; Rickaby, D. A.; Duzgunes, N.; Hillery, C. A.; Konduri, K. S.; Pritchard, K. A., Jr. D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma J. Lipid Res. 2011, 52 (3) 499-508
Coe, H.; Michalak, M. Calcium binding chaperones of the endoplasmic reticulum Gen. Physiol. Biophys. 2009, 28 (Spec No Focus) F96-F103
Kypreou, K. P.; Kavvadas, P.; Karamessinis, P.; Peroulis, M.; Alberti, A.; Sideras, P.; Psarras, S.; Capetanaki, Y.; Politis, P. K.; Charonis, A. S. Altered expression of calreticulin during the development of fibrosis Proteomics 2008, 8 (12) 2407-19
Kelsen, S. G.; Duan, X.; Ji, R.; Perez, O.; Liu, C.; Merali, S. Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach Am. J. Respir. Cell Mol. Biol. 2008, 38 (5) 541-50 (Pubitemid 351758672)
Gardai, S. J.; McPhillips, K. A.; Frasch, S. C.; Janssen, W. J.; Starefeldt, A.; Murphy-Ullrich, J. E.; Bratton, D. L.; Oldenborg, P. A.; Michalak, M.; Henson, P. M. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte Cell 2005, 123 (2) 321-34 (Pubitemid 41457220)
