title: MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets.
abstract: BACKGROUND
  miRNAs are now recognized as key regulator elements in gene expression. Although they have been associated with a number of human diseases, their implication in acute and chronic asthma and their association with lung remodelling have never been thoroughly investigated.
  
  
  RESULTS
  In order to establish a miRNAs expression profile in lung tissue, mice were sensitized and challenged with ovalbumin mimicking acute, intermediate and chronic human asthma. Levels of lung miRNAs were profiled by microarray and in silico analyses were performed to identify potential mRNA targets and to point out signalling pathways and biological processes regulated by miRNA-dependent mechanisms. Fifty-eight, 66 and 75 miRNAs were found to be significantly modulated at short-, intermediate- and long-term challenge, respectively. Inverse correlation with the expression of potential mRNA targets identified mmu-miR-146b, -223, -29b, -29c, -483, -574-5p, -672 and -690 as the best candidates for an active implication in asthma pathogenesis. A functional validation assay was performed by cotransfecting in human lung fibroblasts (WI26) synthetic miRNAs and engineered expression constructs containing the coding sequence of luciferase upstream of the 3'UTR of various potential mRNA targets. The bioinformatics analysis identified miRNA-linked regulation of several signalling pathways, as matrix metalloproteinases, inflammatory response and TGF-β signalling, and biological processes, including apoptosis and inflammation.
  
  
  CONCLUSIONS
  This study highlights that specific miRNAs are likely to be involved in asthma disease and could represent a valuable resource both for biological makers identification and for unveiling mechanisms underlying the pathogenesis of asthma.
authors.affiliation: GIGA-Research, Laboratory of Connective Tissues Biology, University of Liège, Liège, Belgium.
authors.forename: Nancy
authors.initials: N
authors.lastname: Garbacki
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Di Valentin
authors.forename: Vân Anh
authors.initials: VA
authors.lastname: Huynh-Thu
authors.forename: Pierre
authors.initials: P
authors.lastname: Geurts
authors.forename: Alexandre
authors.initials: A
authors.lastname: Irrthum
authors.forename: Céline
authors.initials: C
authors.lastname: Crahay
authors.forename: Thierry
authors.initials: T
authors.lastname: Arnould
authors.forename: Christophe
authors.initials: C
authors.lastname: Deroanne
authors.forename: Jacques
authors.initials: J
authors.lastname: Piette
authors.forename: Didier
authors.initials: D
authors.lastname: Cataldo
authors.forename: Alain
authors.initials: A
authors.lastname: Colige
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics*; D019295:Computational Biology; D020869:Gene Expression Profiling / Q000379:methods*; D007249:Inflammation / Q000235:genetics; D008168:Lung / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000032:analysis*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D035683:MicroRNAs