MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets.
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. METHODOLOGY/PRINC...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3030602?pdf=render |
| _version_ | 1818177155771662336 |
|---|---|
| author | Nancy Garbacki Emmanuel Di Valentin Vân Anh Huynh-Thu Pierre Geurts Alexandre Irrthum Céline Crahay Thierry Arnould Christophe Deroanne Jacques Piette Didier Cataldo Alain Colige |
| author_facet | Nancy Garbacki Emmanuel Di Valentin Vân Anh Huynh-Thu Pierre Geurts Alexandre Irrthum Céline Crahay Thierry Arnould Christophe Deroanne Jacques Piette Didier Cataldo Alain Colige |
| author_sort | Nancy Garbacki |
| collection | DOAJ |
| description | 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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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. |
| first_indexed | 2024-12-11T20:27:36Z |
| format | Article |
| id | doaj.art-6c43df40ffd64c46bf754e41c6af9a1a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T20:27:36Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6c43df40ffd64c46bf754e41c6af9a1a2022-12-22T00:51:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1650910.1371/journal.pone.0016509MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets.Nancy GarbackiEmmanuel Di ValentinVân Anh Huynh-ThuPierre GeurtsAlexandre IrrthumCéline CrahayThierry ArnouldChristophe DeroanneJacques PietteDidier CataldoAlain ColigeBACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.http://europepmc.org/articles/PMC3030602?pdf=render |
| spellingShingle | Nancy Garbacki Emmanuel Di Valentin Vân Anh Huynh-Thu Pierre Geurts Alexandre Irrthum Céline Crahay Thierry Arnould Christophe Deroanne Jacques Piette Didier Cataldo Alain Colige MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets. PLoS ONE |
| title | MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets. |
| title_full | MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets. |
| title_fullStr | MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets. |
| title_full_unstemmed | MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets. |
| title_short | MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets. |
| title_sort | micrornas profiling in murine models of acute and chronic asthma a relationship with mrnas targets |
| url | http://europepmc.org/articles/PMC3030602?pdf=render |
| work_keys_str_mv | AT nancygarbacki micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT emmanueldivalentin micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT vananhhuynhthu micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT pierregeurts micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT alexandreirrthum micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT celinecrahay micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT thierryarnould micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT christophederoanne micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT jacquespiette micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT didiercataldo micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets AT alaincolige micrornasprofilinginmurinemodelsofacuteandchronicasthmaarelationshipwithmrnastargets |