Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human psoriasis patient matched lesion and normal tissue vs. normal controls - type i interferon: potential therapeutic target for psoriasis?

ABSTRACT: We observed robust overexpression of type I interferon (IFN)-inducible genes and genomic signatures that indicate T cell and dendritic cell infiltration in lesional skin. Up-regulation of mRNAs for IFN-a subtypes was observed in lesional skin compared with nonlesional skin. Enrichment of mature dendritic cells and 2 type I IFN-inducible proteins, STAT1 and ISG15, were observed in the majority of lesional skin biopsies. Concordant overexpression of IFN-c and TNF-a inducible gene signatures occurred at the same disease sites. Experiment Overall Design: A total of 82 Affymetrix HGU133 Plus arrays were run on 54 total subjects. This includes: skin biopsy samples from 21 normal healthy donors (Normal-1 to Normal-21), 56 skin biopsy samples from 28 psoriasis patients who had match lesional and uninvolved (non-lesional) tissue (NS-1/LS-1 to NS-9/LS-9, NS-11/LS-11 to NS-14/LS-14, and NS-16/LS-16 to NS-30/LS-30), and 5 samples from psoriasis patients that only provided lesional skin biopsies (LS-10, LS-15, and LS-31 to LS-33).

ORGANISM(S): Homo sapiens

SUBMITTER: Brandon Higgs

PROVIDER: E-GEOD-14905 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Type I interferon: potential therapeutic target for psoriasis?

Yao Yihong Y Richman Laura L Morehouse Chris C de los Reyes Melissa M Higgs Brandon W BW Boutrin Anmarie A White Barbara B Coyle Anthony A Krueger James J Kiener Peter A PA Jallal Bahija B

PloS one 20080716 7

<h4>Background</h4>Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation. To better understand the pathogenesis of this disease and identify potential mediators, we used whole genome array analysis to profile paired lesional and nonlesional psoriatic skin and skin from healthy donors.<h4>Methodology/principal findings</h4>We observed robust overexpression of type I interferon (IFN)-inducible genes a ...[more]

PMID: 18648529

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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.

Dataset Information

Transcription profiling of human psoriasis patient matched lesion and normal tissue vs. normal controls - type i interferon: potential therapeutic target for psoriasis?

Publications

Type I interferon: potential therapeutic target for psoriasis?

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