Abstract
BackgroundPsoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis.MethodsThe study was to elucidate the pathogenesis of PV by quantitative proteomic analysis of skin lesion biopsies of PV and healthy tissues with tandem mass tags (TMTs) coupled with liquid chromatography–mass spectrometry (LC–MS)/MS.ResultsA total of 4562 differentially expressed proteins (DEPs) between PV lesional tissues (n = 11) and healthy tissues (n = 11) were identified, of which 299 were upregulated and 206 were downregulated using |fold change| > 1.3 as the cutoff threshold. The Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEPs were mainly enriched in the activation of immune cells (drug metabolism pathway, NOD-like pathway, and IL-17 pathway), cell proliferation (ribosomal pathway, DNA replication pathway, and base replication pathway), metabolism-related pathways (fatty acid biosynthesis and metabolism, PPAR pathway, glycerophospholipid metabolism, and cortisol synthesis and breakdown), and glandular secretion (saliva secretion, gastric acid secretion, and pancreatic fluid secretion). Thirteen DEPs that were relatively highly expressed in the drug metabolism pathway were validated with parallel reaction monitoring (PRM), of which MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 were highly expressed in PV, whereas CES1, MAOB, MGST1, and GSTT1 were less expressed in PV.ConclusionsThese findings confirmed that these proteins participate in the drug metabolism-other enzyme pathways and play crucial roles in the activation and proliferation of immune cells in the pathogenesis of PV.
Highlights
Psoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis
Swindell et al [7] used the method of Label-free GeLC–MS/MS and LTQ-Orbitrapnano liquid chromatography–mass spectrometry (LC–MS)/MS finding that 748 proteins had differential levels between psoriatic lesional and non-lesional biopsies, including those with concordant and discordant mRNA changes, and most of which were targeted by IL-17A.Tandem mass tags (TMTs) are used in a quantitative proteomic approach that allows the quick identification and quantitation of thousands of proteins [8,9,10] to better understand the pathogenesis of diseases
Gene Ontology (GO) analysis of differentially expressed proteins (DEPs) The DEPs were assigned by GOSeq into three groups: biological process (BP), cellular component (CC), and molecular function (MF)
Summary
Psoriasis vulgaris (PV) is a chronic autoimmune inflammatory disease with epidermal hyperkeratosis and parakeratosis. The development of multiple “-omic”-based approaches has provided an effective way to identify and characterize proteins that are involved in the pathogenesis of PV. Swindell et al [7] used the method of Label-free GeLC–MS/MS and LTQ-Orbitrapnano LC–MS/MS finding that 748 proteins had differential levels between psoriatic lesional and non-lesional biopsies, including those with concordant and discordant mRNA changes, and most of which were targeted by IL-17A.Tandem mass tags (TMTs) are used in a quantitative proteomic approach that allows the quick identification and quantitation of thousands of proteins [8,9,10] to better understand the pathogenesis of diseases. We characterized differentially expressed proteins (DEPs) with TMT-based quantitative proteomic analysis of peripheral blood mononuclear cells from patients with PV [11]. TMT-based quantitative proteomic analysis provides new avenues for better understanding of the pathogenesis of PV at the protein level
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