Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Identifying interferon-stimulated genes enriched in multiple tissues of Irgm1-/- mice

ABSTRACT: We observed enhanced epithelial proliferation secondary to elevated Type I IFNs in multiple tissues of Irgm1-/- mice. We discovered that Type I IFNs signaled through macrophages to promote this epithelial hyperproliferation. To determine candidate factors that could play a role in this process, we performed whole genome microarray analysis of salivary gland, small intestine, and isolated colonic macrophages of Irgm1-/- mice and C57BL/6 WT controls. Genes enriched in at least 2 of the 3 sample sources were then screened for the ability to augment epithelial proliferation in vitro. RNA was extracted from three (small intestine and isolated colonic macrophage samples) or four (salivary gland samples) mice of each genotype (Irgm1-/- and WT). Both male and female six to nine week-old mice were used.

ORGANISM(S): Mus musculus

SUBMITTER: Lulu Sun

PROVIDER: E-GEOD-59603 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: We have previously used the rat 4 day Complete Freund's Adjuvant (CFA) model to screen compounds with potential to reduce osteoarthritic pain. The aim of this study was to identify genes altered in this model of osteoarthritic pain and use this information to infer analgesic potential of compounds based on their own gene expression profiles using the Connectivity Map approach. Results: Using microarrays, we identified differentially expressed genes in L4 and L5 dorsal root ganglia (DRG) from rats that had received intraplantar CFA for 4 days compared to matched, untreated control animals. Analysis of these data indicated that the two groups were distinguishable by differences in genes important in immune responses, nerve growth and regeneration. This list of differentially expressed genes defined a âCFA signatureâ. We used the Connectivity Map approach to identify pharmacologic agents in the Broad Institute Build02 database that had gene expression signatures that were inversely related (ânegatively connectedâ) with our CFA signature. To test the predictive nature of the Connectivity Map methodology, we tested phenoxybenzamine (an alpha adrenergic receptor antagonist) â one of the most negatively connected compounds identified in this database - for analgesic activity in the CFA model. Our results indicate that at 10mg/kg, phenoxybenzamine demonstrated analgesia comparable to that of Naproxen in this model. Conclusion: Evaluation of phenoxybenzamine-induced analgesia in the current study lends support to the utility of the Connectivity Map approach for identifying compounds with analgesic properties in the CFA model. A naive (control) group of rats (n = 6) and a group of rats injected with CFA (n = 6) were used for gene expression profiling experiments. One animal from the control group did not yield sufficient amount of RNA for microarray and thus was omitted from further processing. In total, 5 microarrays each from the 5 animals in the control group, and 6 microarrays each from the 6 animals in the CFA group were analyzed.

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Identifying interferon-stimulated genes enriched in multiple tissues of Irgm1-/- mice

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