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      Proteomics in Psoriasis

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          Abstract

          Psoriasis has been thought to be driven primarily by innate and adaptive immune systems that can be modified by genetic and environmental factors. Complex interplay between inflammatory cytokines and T-cells, especially Th1 and Th17 cells, leads to abnormal cell proliferation and psoriatic skin lesions. Nevertheless, such mechanisms do not entirely represent the pathogenesis of psoriasis. Moreover, earlier and better biomarkers in diagnostics, prognostics, and monitoring therapeutic outcomes of psoriasis are still needed. During the last two decades, proteomics (a systematic analysis of proteins for their identities, quantities, and functions) has been widely employed to psoriatic research. This review summarizes and discusses all of the previous studies that applied various modalities of proteomics technologies to psoriatic skin disease. The data obtained from such studies have led to (i) novel mechanisms and new hypotheses of the disease pathogenesis; (ii) biomarker discovery for diagnostics and prognostics; and (iii) proteome profiling for monitoring treatment efficacy and drug-induced toxicities.

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          Most cited references42

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          S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3.

          Psoriasis is a common heterogeneous inflammatory skin disease with a complex pathophysiology and limited treatment options. Here we performed proteomic analyses of human psoriatic epidermis and found S100A8-S100A9, also called calprotectin, as the most upregulated proteins, followed by the complement component C3. Both S100A8-S100A9 and C3 are specifically expressed in lesional psoriatic skin. S100A9 is shown here to function as a chromatin component modulating C3 expression in mouse and human cells by binding to a region upstream of the C3 start site. When S100A9 was genetically deleted in mouse models of skin inflammation, the psoriasis-like skin disease and inflammation were strongly attenuated, with a mild immune infiltrate and decreased amounts of C3. In addition, inhibition of C3 in the mouse model strongly reduced the inflammatory skin disease. Thus, S100A8-S100A9 can regulate C3 at the nuclear level and present potential new therapeutic targets for psoriasis. Copyright © 2013 Elsevier Inc. All rights reserved.
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            β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis.

            IL-17A is a key driver of human autoimmune diseases, particularly psoriasis.
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              Proteogenomic analysis of psoriasis reveals discordant and concordant changes in mRNA and protein abundance

              Background Psoriasis is a chronic disease characterized by the development of scaly red skin lesions and possible co-morbid conditions. The psoriasis lesional skin transcriptome has been extensively investigated, but mRNA levels do not necessarily reflect protein abundance. The purpose of this study was therefore to compare differential expression patterns of mRNA and protein in psoriasis lesions. Methods Lesional (PP) and uninvolved (PN) skin samples from 14 patients were analyzed using high-throughput complementary DNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results We identified 4122 differentially expressed genes (DEGs) along with 748 differentially expressed proteins (DEPs). Global shifts in mRNA were modestly correlated with changes in protein abundance (r = 0.40). We identified similar numbers of increased and decreased DEGs, but 4-fold more increased than decreased DEPs. Ribosomal subunit and translation proteins were elevated within lesions, without a corresponding shift in mRNA expression (RPL3, RPS8, RPL11). We identified 209 differentially expressed genes/proteins (DEGPs) with corresponding trends at the transcriptome and proteome levels. Most DEGPs were similarly altered in at least one other skin disease. Psoriasis-specific and non-specific DEGPs had distinct cytokine-response patterns, with only the former showing disproportionate induction by IL-17A in cultured keratinocytes. Conclusions Our findings reveal global imbalance between the number of increased and decreased proteins in psoriasis lesions, consistent with heightened translation. This effect could not have been discerned from mRNA profiling data alone. High-confidence DEGPs were identified through transcriptome-proteome integration. By distinguishing between psoriasis-specific and non-specific DEGPs, our analysis uncovered new functional insights that would otherwise have been overlooked. Electronic supplementary material The online version of this article (doi:10.1186/s13073-015-0208-5) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                06 March 2019
                March 2019
                : 20
                : 5
                : 1141
                Affiliations
                [1 ]Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; leenajim@ 123456gmail.com (L.C.); anonaemew@ 123456gmail.com (N.C.); doctornarumol@ 123456gmail.com (N.S.-A.); chanisada@ 123456hotmail.com (C.W.)
                [2 ]Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
                Author notes
                [* ]Correspondence: thongboonkerd@ 123456dr.com or vthongbo@ 123456yahoo.com ; Tel.: +66-2-4192850
                Article
                ijms-20-01141
                10.3390/ijms20051141
                6429319
                30845706
                1a60f730-1781-4a9d-a873-f53b05287085
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 January 2019
                : 02 March 2019
                Categories
                Review

                Molecular biology
                biomarker discovery,dermatology,diagnostics,prognostics,mass spectrometry,proteome,psoriatic skin

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