Lipidomics profiling reveals the role of glycerophospholipid metabolism in psoriasis

Abstract Psoriasis is a common and chronic inflammatory skin disease that is complicated by gene–environment interactions. Although genomic, transcriptomic, and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes such as cell proliferation, apoptosis, immunity, angiogenesis, and inflammation. In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and to identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-tandem quadrupole mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and analyzed. Statistical analysis was applied to find different metabolites between the disease and healthy groups. In addition, enzyme-linked immunosorbent assay was performed to validate differentially expressed lipids in psoriatic patient plasma. Finally, we identified differential expression of several lipids including lysophosphatidic acid (LPA), lysophosphatidylcholine (LysoPC), phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidic acid (PA); among these metabolites, LPA, LysoPC, and PA were significantly increased, while PC and PI were down-regulated in psoriasis patients. We found that elements of glycerophospholipid metabolism such as LPA, LysoPC, PA, PI, and PC were significantly altered in the plasma of psoriatic patients; this study characterizes the circulating lipids in psoriatic patients and provides novel insight into the role of lipids in psoriasis.

[1]  Siqi Liu,et al.  metaX: a flexible and comprehensive software for processing metabolomics data , 2017, BMC Bioinformatics.

[2]  Jianguo Xia,et al.  Using MetaboAnalyst 3.0 for Comprehensive Metabolomics Data Analysis , 2016, Current protocols in bioinformatics.

[3]  N. Arora,et al.  Lysophosphatidylcholine plays critical role in allergic airway disease manifestation , 2016, Scientific Reports.

[4]  A. Indra,et al.  Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans , 2016, Expert review of proteomics.

[5]  D. Gladman,et al.  The Incidence and Predictors of Infection in Psoriasis and Psoriatic Arthritis: Results from Longitudinal Observational Cohorts , 2016, The Journal of Rheumatology.

[6]  Sai-nan Zhu,et al.  Characterization of the abnormal lipid profile in Chinese patients with psoriasis. , 2015, International journal of clinical and experimental pathology.

[7]  Shan Jiang,et al.  Biomarkers of An Autoimmune Skin Disease—Psoriasis , 2015, Genom. Proteom. Bioinform..

[8]  A. Kyrgidis,et al.  IL-17A, IL-22, and IL-23 as Markers of Psoriasis Activity , 2015, Journal of cutaneous medicine and surgery.

[9]  G. J. Harry,et al.  Autotaxin Downregulates LPS‐Induced Microglia Activation and Pro‐Inflammatory Cytokines Production , 2014, Journal of cellular biochemistry.

[10]  M. Huse Lipid-based patterning of the immunological synapse. , 2014, Biochemical Society transactions.

[11]  Giridharan Gokulrangan,et al.  Proteomics of Skin Proteins in Psoriasis: From Discovery and Verification in a Mouse Model to Confirmation in Humans* , 2014, Molecular & Cellular Proteomics.

[12]  J L Gómez-Ariza,et al.  Metabolomic study of lipids in serum for biomarker discovery in Alzheimer's disease using direct infusion mass spectrometry. , 2014, Journal of pharmaceutical and biomedical analysis.

[13]  André Nadler,et al.  Caged lipids as tools for investigating cellular signaling. , 2014, Biochimica et biophysica acta.

[14]  M. Ratajczak,et al.  Bioactive Lipids, LPC and LPA, Are Novel Prometastatic Factors and Their Tissue Levels Increase in Response to Radio/Chemotherapy , 2014, Molecular Cancer Research.

[15]  Elaine Holmes,et al.  Objective set of criteria for optimization of sample preparation procedures for ultra-high throughput untargeted blood plasma lipid profiling by ultra performance liquid chromatography-mass spectrometry. , 2014, Analytical chemistry.

[16]  M. Blumenberg Skinomics: past, present and future for diagnostic microarray studies in dermatology , 2013, Expert review of molecular diagnostics.

[17]  M. Huse,et al.  From lipid second messengers to molecular motors: microtubule‐organizing center reorientation in T cells , 2013, Immunological reviews.

[18]  Christoph Steinbeck,et al.  The role of reporting standards for metabolite annotation and identification in metabolomic studies , 2013, GigaScience.

[19]  D. A. Foster Phosphatidic acid and lipid-sensing by mTOR , 2013, Trends in Endocrinology & Metabolism.

[20]  David A. Martin,et al.  The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. , 2013, Trends in immunology.

[21]  Rosa Parisi,et al.  Global epidemiology of psoriasis: a systematic review of incidence and prevalence. , 2013, The Journal of investigative dermatology.

[22]  T. Tsukahara The Role of PPARγ in the Transcriptional Control by Agonists and Antagonists , 2012, PPAR research.

[23]  W. Kong,et al.  Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice , 2012, PPAR research.

[24]  R. Coleman,et al.  Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling , 2012, Proceedings of the National Academy of Sciences.

[25]  T. Lotti,et al.  Mucosal psoriasis: a new insight toward a systemic inflammatory disease , 2011, International journal of dermatology.

[26]  Claudio J. Verzilli,et al.  Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration , 2011, European heart journal.

[27]  Mee-Sup Yoon,et al.  Phosphatidic Acid Activates Mammalian Target of Rapamycin Complex 1 (mTORC1) Kinase by Displacing FK506 Binding Protein 38 (FKBP38) and Exerting an Allosteric Effect* , 2011, The Journal of Biological Chemistry.

[28]  Joshua D. Knowles,et al.  Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry , 2011, Nature Protocols.

[29]  Chunyu Liu,et al.  Removing Batch Effects in Analysis of Expression Microarray Data: An Evaluation of Six Batch Adjustment Methods , 2011, PloS one.

[30]  Terry K. Smith,et al.  The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine , 2010, IUBMB life.

[31]  D. A. Foster Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells. , 2009, Biochimica et biophysica acta.

[32]  J. Kabarowski G2A and LPC: regulatory functions in immunity. , 2009, Prostaglandins & other lipid mediators.

[33]  A. Morris,et al.  Regulation of blood and vascular cell function by bioactive lysophospholipids , 2009, Journal of thrombosis and haemostasis : JTH.

[34]  F. Nestle,et al.  The IL-23/Th17 axis in the immunopathogenesis of psoriasis. , 2009, The Journal of investigative dermatology.

[35]  A. Sheikh,et al.  Lysophosphatidylcholine induces glial cell activation: Role of rho kinase , 2009, Glia.

[36]  S. Gabriel,et al.  Incidence and clinical predictors of psoriatic arthritis in patients with psoriasis: a population-based study. , 2009, Arthritis and rheumatism.

[37]  Meihong Chen,et al.  Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells. , 2008, Biochemical and biophysical research communications.

[38]  P. Robin,et al.  Role of lysophosphatidic acid in the regulation of uterine leiomyoma cell proliferation by phospholipase D and autotaxin Published, JLR Papers in Press, November 16, 2007. , 2008, Journal of Lipid Research.

[39]  R. García-Becerra,et al.  Regulation of LPA receptor function by estrogens. , 2008, Biochimica et biophysica acta.

[40]  Age K. Smilde,et al.  UvA-DARE ( Digital Academic Repository ) Assessment of PLSDA cross validation , 2008 .

[41]  J. Balsinde,et al.  Group V Phospholipase A2-Derived Lysophosphatidylcholine Mediates Cyclooxygenase-2 Induction in Lipopolysaccharide-Stimulated Macrophages1 , 2007, The Journal of Immunology.

[42]  J. Lykkesfeldt Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. , 2007, Clinica chimica acta; international journal of clinical chemistry.

[43]  W. Moolenaar,et al.  Regulation and biological activities of the autotaxin-LPA axis. , 2007, Progress in lipid research.

[44]  Ying Zhang,et al.  HMDB: the Human Metabolome Database , 2007, Nucleic Acids Res..

[45]  David W. Russell,et al.  LMSD: LIPID MAPS structure database , 2006, Nucleic Acids Res..

[46]  I. Wilson,et al.  A pragmatic and readily implemented quality control strategy for HPLC-MS and GC-MS-based metabonomic analysis. , 2006, The Analyst.

[47]  C. McMaster,et al.  Glycerophosphocholine Catabolism as a New Route for Choline Formation for Phosphatidylcholine Synthesis by the Kennedy Pathway* , 2005, Journal of Biological Chemistry.

[48]  M. Wenk The emerging field of lipidomics , 2005, Nature Reviews Drug Discovery.

[49]  Li V. Yang,et al.  Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A. , 2005, Blood.

[50]  G. Carman,et al.  Regulation of Phospholipid Synthesis in the Yeast cki1Δ eki1Δ Mutant Defective in the Kennedy Pathway , 2004, Journal of Biological Chemistry.

[51]  G. Carman,et al.  Regulation of Phospholipid Synthesis in the Yeastcki1Δeki1Δ Mutant Defective in the Kennedy Pathway: THECHO1-ENCODED PHOSPHATIDYLSERINE SYNTHASE IS REGULATED BY mRNA STABILITY , 2004 .

[52]  Chunxiang Zhang,et al.  Lysophosphatidic Acid Induces Neointima Formation Through PPARγ Activation , 2004, The Journal of experimental medicine.

[53]  M. Barker,et al.  Partial least squares for discrimination , 2003 .

[54]  Daniel L Baker,et al.  Plasma lysophosphatidic acid concentration and ovarian cancer. , 2002, JAMA.

[55]  D. Baker,et al.  Multiple Mechanisms Linked to Platelet Activation Result in Lysophosphatidic Acid and Sphingosine 1-Phosphate Generation in Blood* , 2002, The Journal of Biological Chemistry.

[56]  K. Hirata,et al.  Signaling mechanism underlying COX-2 induction by lysophosphatidylcholine. , 2001, Biochemical and biophysical research communications.

[57]  Y. Shoenfeld,et al.  Atherosclerosis-related markers in systemic lupus erythematosus patients: The role of humoral immunity in enhanced atherogenesis , 1999, Lupus.

[58]  Y. Kitajima,et al.  Lipocortin I (annexin I) is preferentially localized on the plasma membrane in keratinocytes of psoriatic lesional epidermis as shown by immunofluorescence microscopy. , 1991, The Journal of investigative dermatology.

[59]  U. Beuers,et al.  Lysophosphatidic acid and signaling in sensory neurons. , 2015, Biochimica et biophysica acta.

[60]  A. Gottlieb,et al.  Research gaps in psoriasis: opportunities for future studies. , 2014, Journal of the American Academy of Dermatology.

[61]  F. Toyoda,et al.  Lysophosphatidylcholine enhances I(Ks) currents in cardiac myocytes through activation of G protein, PKC and Rho signaling pathways. , 2011, Journal of molecular and cellular cardiology.

[62]  Adrian Hernandez,et al.  Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. , 2009, American heart journal.

[63]  Eoin Fahy,et al.  Bioinformatics for lipidomics. , 2007, Methods in enzymology.