New asthma biomarkers: lessons from murine models of acute and chronic asthma.
Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the present study was to unveil new mediators in asthma to better understand pathophysiology and propose or validate new potential therapeutic targets. A mouse model of asthma mimicking acute or chronic asthma disease was used to select genes undergoing a modulation in both acute and chronic conditions. Mice were exposed to ovalbumin or PBS for 1, 5, and 10 wk [short-, intermediate-, and long-term model (ST, IT, and LT)], and gene expression in the lung was studied using an Affymetrix 430 2.0 genome-wide microarray and further confirmed by RT-PCR and immunohistochemistry for selected targets. We report that 598, 1,406, and 117 genes were upregulated and 490, 153, 321 downregulated at ST, IT, and LT, respectively. Genes related to mucous secretion displayed a progressively amplified expression during the allergen exposure protocol, whereas genes corresponding to growth and differentiation factors, matrix metalloproteinases, and collagens were mainly upregulated at IT. By contrast, genes related to cell division were upregulated at ST and IT and were downregulated at LT. In this study, besides confirming that Arg1, Slc26a4, Ear11, and Mmp12 genes are highly modulated throughout the asthma pathology, we show for the first time that Agr2, Scin, and Cd209e genes are overexpressed throughout the allergen exposure and might therefore be considered as suitable new potential targets for the treatment of asthma.
Di Valentin
Emmanuel
E
GIGA-Research Laboratory of Fundamental Virology and Immunology, Univ. of Liège, B-4000 Liège, Belgium. edivalentin@ulg.ac.be
Crahay
Céline
C
Garbacki
Nancy
N
Hennuy
Benoit
B
Guéders
Maud
M
Noël
Agnès
A
Foidart
Jean-Michel
JM
Grooten
Johan
J
Colige
Alain
A
Piette
Jacques
J
Cataldo
Didier
D
D000208:Acute Disease; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007124:Immunoenzyme Techniques; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins; D010047:Ovalbumin / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018260:Gelsolin; D037181:Lectins, C-Type; D009088:Mucoproteins; D015513:Oncogene Proteins; D010047:Ovalbumin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C526445:Agr2 protein, mouse; C065395:scinderin