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Whole lung transcriptomics of a house dust mite model of mild/moderate asthma

ABSTRACT: Purpose: Identify whole lung gene expression patterns in a house dust mite model of mild/moderate asthma Methods: Lung gene expression profiles of 10 week old BALB/c female mice were generated by ribosome-depleted, 150 nt, paired-end, stranded RNA-seq with Illumina HiSeq v4. Sequence reads that passed quality filters after trimming were analyzed with Sailfish-cir to identify linear RNAs and circular RNAs. Differential expression of linear RNAs was assessed with Deseq2 . QRT–PCR validation was performed using TaqMan and SYBR Green methods. Results: 100 million sequence reads per sample were mapped to the mouse genome (build mm10) using Sailfish-cir to identify linear and circular RNA transcripts. Pathway analysis of differentially expressed genes identified upregulation of gene sets for human asthma, mouse lung allergic inflammation, Muc5ac regulated genes and smooth muscle genes after allergic sensitization. Gene level exppression in each asthma-related pathway was reduced by the miR-145 antagonist. The miR-145 antagonist and several nontargeting oligos also upregulated interferon signaling pathways suggesting a general antiinflammatory effect of LNA/DNA oligos in the lung. Conclusions: Lung-directed delivery of LNA/DNA oligonucleotides with cationic lipid nanoparticles is an efffective means to prevent inflammatory gene expression in a house dust mite model of mild/moderate asthma.

ORGANISM(S): Mus musculus

PROVIDER: GSE132263 | GEO | 2019/06/06

REPOSITORIES: GEO

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Project description:Background: In asthma, airway epithelium remodeling can already be detected during childhood, and epithelial cells are more susceptible to virus and oxidative stress. Their exact role in natural history and severity of children allergic respiratory disease remains however surprisingly unexplored. Aim: To analyze dysfunctions of epithelium in dust mite allergic respiratory disease (rhinitis ¬± asthma) in children. Methods: Expression profilings of nasal epithelial cells collected by brushing were performed on Affymetrix Hugene 1.0 ST arrays. All allergic patients were sensitized to dust mite. 19 patients had an isolated allergic rhinitis (AR). 14 patients had AR associated with asthma. Patients were compared to 12 controls, their severity and control being assessed according to NAEPP and ARIA criteria. Infections by respiratory viruses were excluded by real-time PCR measurements. Results: 61 probes were able to distinguish allergic rhinitis children from healthy controls. A majority of these probes was under the control of Th2 cytokines, as evidenced by parallel experiments performed on primary cultures of nasal epithelial cells. In uncontrolled asthmatic patients, we observed not only an enhanced expression of these Th2-responsive transcripts, but also a down-regulation of interferon-responsive genes. Conclusion: Our study identifies a Th2 driven epithelial phenotype common to all dust mite allergic children. Besides, it suggests that epithelium is involved in the severity of the disease. Expression profiles observed in uncontrolled asthmatic patients suggest that severity of asthma is linked at the same time to atopy and to impaired viral response. Nasal epithelium gene expression profiling of dust mite allergic children with isolated rhinitis, rhinitis associated with asthma and controls. 38 samples classified in 4 categories : 14 isolated rhinitis (R), 6 rhinitis with uncontrolled asthma (UA), 7 rhinitis with controlled asthma (CA) and 11 healthy subjects (C )

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Whole lung transcriptomics of a house dust mite model of mild/moderate asthma

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