Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-13355
PROVIDER: PRJNA138243 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The efficacy of monoclonal antibodies against either interleukin (IL)-17 or the IL-17 receptor in psoriasis therapy provides strong evidence that IL-17 is the major inflammatory mediation in this disease. However, how IL-17 induces epidermal hyperplasia in psoriasis remains largely unknown. Here, we show that IL-17 actives NF-kB in keratinocytes and initiates the NF-kB-dependent transcription of microRNA-31 (miR-31), one of the most abundant microRNAs in the epidermis of lesional skin of psoriasis and two related mouse models. Similar to IL-17 deficiency (IL-17-/-), knocking out miR-31 (miR-31-/-) or targeting it by antagomir-31 prevents keratinocytes Ki67 expression and inhibits acanthosis and dermal inflammation in psoriasis mouse model. Moreover, PPP6c, a negative regulator restricting G0/G1 to G2/M phase progression in the cell cycle, is diminished in human psoriatic epidermis and is directly targeted by miR-31. Inhibition of ppp6c is functionally important for the biological effects of miR-31 in the development of epidermal hyperplasia. Thus, our data define IL-17-inducede miR-31 and its target ppp6c as critical factors for hyperproliferative epidermis in psoriasis. Epidermis samples from affected ears derived from 3 CD18hypo PL/J mice (DIS) or normal ears derived from 3 CD18hypo C57BL/6J mice(2128) were used for RNA extraction and hybridization on Affymetrix microarrays. We sought to compare miRNA expression of normal skin from control and lesional skin.
2013-12-31 | E-GEOD-50099 | biostudies-arrayexpress
Project description:Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. Global transcriptional profiling was utilized to evaluate the similarity between human psoriasis and the psoriasis-like phenotypes that develop in five mouse models (K5-Tie2, IMQ, K14-AREG, K5-Stat3C, K5-TGFbeta1) Expression patterns associated with mouse phenotypes were evaluated by comparing lesional skin from transgenic or IMQ-treated mice (n = 2-3) with normal skin obtained from control mice (n = 2-3).
2011-03-03 | E-GEOD-27628 | biostudies-arrayexpress
Project description:Herein we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n=3) were compared with littermate controls (n=3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average P = 0.0082; cystatin A, human orthologue); slc25a5 (average fold change of 46.2 and an average P = 0.0318); serpinb3b (average fold change of 35.6 and an average P = 0.0345; serpinB1, human orthologue); and kallikrein related peptidase 6 (average fold change of 4.7 and an average P = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, P < 0.0001), KLK6 (9.0-fold, P = 0.002), stefin A1 (7.3-fold; P < 0.001) and slc25A5 (1.5-fold; P = 0.05) using qRT-PCR on a second cohort of animals (n=8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; P < 0.05), 29,000-fold (stefinA1; P < 0.01), 322-fold (KLK6; P < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes vs. healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3.0-fold), KLK6 (5.8-fold) and serpinB1 (76-fold; all P < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover slc25a5, cystatin A, KLK6 and serpinB1 protein were all increased in lesional psoriasis skin compared to normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.
2014-10-30 | PXD001387 | Pride
Project description:Gene expression profiling was performed on biopsies of affected and unaffected psoriatic skin and normal skin from seven Japanese patients to obtain insights into the pathways that control this disease. U95A Affymetrix DNA chips that contain oligonucleotide arrays of approximately 12,000 well-characterized human genes were used in the study. The statistical analysis of the Affymetrix data, based on the ranking of the Student-test statistic, revealed a complex regulation of molecular stress and immune gene responses. The majority of the 266 induced-genes in affected and unaffected psoriatic skin were involved with interferon mediation, immunity, cell-adhesion, cytoskeleton restructuring, protein trafficking and degradation, RNA regulation and degradation, signaling transduction, apoptosis and atypical epidermal cellular proliferation and differentiation. The disturbances in the normal protein degradation equilibrium of skin were reflected by the significant increase in the gene expression of various protease inhibitors and proteinases including the induced components of the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved with peptide processing and presentation to T-cells. Some of the upregulated genes, such as TGM1, IVL, CSTA, FABP5 and SPRR, are well known psoriatic markers involved in atypical epidermal cellular organization and differentiation. In the comparison between the affected and unaffected psoriatic skin, the transcription factor JUNB was found at the top of the statistical rankings for the 51 significantly upregulated genes in affected skin, suggesting that it has an important but as yet undefined role in psoriasis. Our gene expression data and analysis suggest that psoriasis is a chronic IFN and T-cell-mediated immune disease of the skin where the imbalance in epidermal cellular structure, growth and differentiation arises from the molecular antiviral stress signals initiating inappropriate immune responses. Experiment Overall Design: Analysis of the expression profile of skin samples for each of three conditions (states) of psoriasis activity Experiment Overall Design: 3 samples were from psoriasis negative individuals (biological replicates) Experiment Overall Design: 4 samples were from psorasis free skin areas of psoriasis active individuals (biological replicates) Experiment Overall Design: 4 samples were from psorasis active skin areas of psoriasis active individuals (biological replicates)
2007-09-20 | E-GEOD-2737 | biostudies-arrayexpress
Project description:Gene expression has been proposed as an intermediate phenotype that can increase power in complex trait gene-mapping studies. Psoriasis, an immune-mediated, inflammatory and hyperproliferative disease of the skin and joints, provides an ideal model system to evaluate this paradigm, as conclusive evidence demonstrates that psoriasis has a genetic basis and the disease tissue is readily accessible. To better understand the complex nature of processes in psoriasis, we characterize gene expression profiles in uninvolved and involved skin from affected individuals as well as normal skin from control individuals. Keywords: disease state analysis
2009-01-25 | GSE13355 | GEO
Project description:Gene expression has been proposed as an intermediate phenotype that can increase power in complex trait gene-mapping studies. Psoriasis, an immune-mediated, inflammatory and hyperproliferative disease of the skin and joints, provides an ideal model system to evaluate this paradigm, as conclusive evidence demonstrates that psoriasis has a genetic basis and the disease tissue is readily accessible. To better understand the complex nature of processes in psoriasis, we characterize gene expression profiles in uninvolved and involved skin from affected individuals as well as normal skin from control individuals. Experiment Overall Design: We extracted total RNA from punch biopsies taken from 58 psoriatic patients and 64 normal healthy controls. Two biopsies were taken from each patient; one 6mm punch biopsy was obtained from lesional skin of each patient (involved sample) and the other from non-lesional skin (uninvolved sample), taken at least 10 cm away from any active plaque. One biopsy was obtained from each healty control. Totally 180 samples were run on Affymetrix HU133 Plus 2.0 microarrays containing >54,000 gene probes. Experiment Overall Design: The raw data from 180 microarrays were processed using the Robust Multichip Average (RMA) method. The expression values in the table were after adjustment of RMA expression values (on the log scale) to account for batch and sex effects. Experiment Overall Design: Definition of abbreviations used in Sample records: NN = normal skin from controls; PN = uninvolved skin from cases; PP = involved skin from cases.
2009-02-01 | E-GEOD-13355 | biostudies-arrayexpress
Project description:Affected and unaffected skin of 4 psoriatic patients and normal skin of 3 psoriasis free individuals
| PRJNA92229 | ENA
Project description:Comparing molecular signatures of psoriasis and eczema in patients co-affected by both diseases provides a comprehensive understanding of disease pathogenesis as well as a diagnostic tool to differentiate these widespread inflammatory skin diseases. In patients affected by both psoriasis and non-atopic or atopic eczema simultaneously (n=24), whole genome expression arrays of psoriasis, eczema, and non-involved skin were performed Arrays MQ_35 and MQ_41 did not pass quality control and thus were not normalized and were excluded from this Series.
2014-05-01 | E-GEOD-57225 | biostudies-arrayexpress
Project description:CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin. Camk4-deficient (Camk4−/−) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice. There are more macrophages and fewer IL-17A+γδ TCR+ cells in the skin of IMQ-treated Camk4−/− mice compared to IMQ-treated WT mice. CaMK4 inhibits IL-10 production by macrophages, thus allowing excessive psoriatic inflammation. Deletion of Camk4 in macrophages alleviates IMQ-induced psoriatic inflammation in mice. In keratinocytes, CaMK4 inhibits apoptosis as well as promotes cell proliferation and the expression of pro-inflammatory genes such as S100A8 and CAMP. Taken together, these data indicate that CaMK4 regulates IMQ-induced psoriasis by sustaining inflammation and provides a potential target for psoriasis treatment.
2022-05-28 | GSE204832 | GEO
Project description:To increase our understanding of psoriasis, we utilized RNA-seq to assay the transcriptomes of skin samples from 3 Tnip1+/+ and 3 Tnip1-/- mice that were treated for two days with imiquimod (IMQ) and performed cross-species analyses with human transcriptome data derived from psoriasis patients and healthy subjects (GSE54456). Intriguingly, the vast majority of genes deregulated in Tnip1-/- mice correlated with their human counterparts, substantiating the interpretation that gene deregulation in Tnip1-/- mice reflects a psoriasis-specific pattern rather than being the consequence of an overall exaggerated inflammatory skin response. Together, the data demonstrate that loss of Tnip1 function leads to genetic susceptibility against IMQ, akin to human disease. As expected, gene ontology (GO) analysis highlighted gene sets known to be affected in psoriasis, such as epidermal development, immune/ defense response, proteolysis and response to wounding.
2016-09-26 | GSE85891 | GEO