Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MicroRNA profiling of cystic fibrosis intestinal disease in mice

ABSTRACT: Cystic fibrosis (CF) intestinal disease is characterized by alterations in processes such as proliferation and apoptosis which are known to be regulated in part by microRNA’s. Herein, we completed microRNA expression profiling of the intestinal tissue from the cystic fibrosis mouse model of cystic fibrosis transmembrane conductance regulator (Cftr) deficient mice (BALBc/J Cftrtm1UNC), relative to that of wildtype littermates, to determine whether changes in microRNA expression level are part of this phenotype. We identified 24 microRNA's to be significantly differentially expressed in tissue from CF mice compared to wildtype, with the higher expression in tissue from CF mice. These data were confirmed with real time PCR measurements. A comparison of the list of genes previously reported to have decreased expression in the BALB x C57BL/6J F2 CF intestine to that of genes putatively targeted by the 24 microRNA’s, determined from target prediction software, revealed 20% of the gene expression profile to overlap with predicted targets. Pathway analysis identified these common genes to function in phosphatase and tensin homolog-, protein kinase A-, phosphoinositide-3 kinase/Akt- and peroxisome proliferator-activated receptor alpha/retinoid X receptor alpha signaling pathways, among others, and through real time PCR experiments genes of these pathways were demonstrated to have lower expression in the BALB CF intestine. We conclude that altered microRNA expression is a feature which putatively influences both metabolic abnormalities and the altered tissue homeostasis component of CF intestinal disease. Two condition experiment, Balbc/J Cftrtm1UNC -/- (Cystic Fibrosis (CF) Mice) and Balbc/J Cftrtm1UNC +/+ (Wild Type (WT) Mice). Biological Replicates: 7 WT, 8CF. Ileum Tissue.

ORGANISM(S): Mus musculus

SUBMITTER: Christina Haston

PROVIDER: E-GEOD-19621 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Pulmonary fibrosis is a disease characterized by inflammatory cell infiltration, scar formation, deposition of extracellular matrix, alveolar epithelial cell injury and hyperplasia. To determine if alterations in microRNA expression contribute to these phenotypes, microRNA expression profiling of the lungs from bleomycin treated C57Bl/6J mice, relative to that of untreated controls, was undertaken. Mice were treated at 8 weeks old with 100 Units/kg of bleomycin delivered subcutaneously with osmotic minipumps. At 42 days post treatment mice were euthanized and lung microRNA isolated. We identified 11 microRNA's to be significantly differentially expressed (FDR threshold of 0.01) in the lungs of bleomycin treated mice and confirmed these data with real time PCR measurements. These included bleomycin upregulated miR-34a, 335-5p, 207, 21, 301a, 146b, 199a-5p, and 449a and bleomycin downregulated miR-151-3p, 26a and 676. We have previously shown that 1558 genes are differentially expressed in the lungs of bleomycin treated mice. Of the 1412 targets of upregulated microRNAs, 142 were confirmed to be downregulated in the gene expression profile (GEP). Of the 583 targets of downregulated microRNAs, 53 were confirmed to be upregulated in the gene expression profile. Pathway analysis of the microRNA targets and GEP overlapping genes indicated that altered microRNA expression is associated with cellular development, cellular growth, cellular proliferation and changed tissue/cell morphology. Specific pathways include HGF signaling, Cholecystokinin/Gastrin-mediated signaling, Endothelin-1 signaling, RAR activation, Phospholipase C signaling and IGF1 signaling. We conclude that altered microRNA expression is a feature of pulmonary fibrosis which putatively influences components of the altered airway disease. Two condition study, C57Bl/6J mice treated with 100 Units/kg bleomycin and untreated controls. Biological replicated n =3 for each group. Left lung tissue.

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MicroRNA profiling of cystic fibrosis intestinal disease in mice

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