Abstract
Background
Psoriasis is an immune-mediated, inflammatory and hyperproliferative disease of the
skin and joints. The cause of psoriasis is still unknown. The fundamental feature
of the disease is the hyperproliferation of keratinocytes and the recruitment of cells
from the immune system in the region of the affected skin, which leads to deregulation
of many well-known gene expressions.
Objective
Based on data mining and bioinformatic scripting, here we show a new dimension of
the effect of psoriasis at the genomic level.
Methods
Using our own pipeline of scripts in Perl and MySql and based on the freely available
NCBI Gene Expression Omnibus (GEO) database: DataSet Record GDS4602 (Series GSE13355),
we explore the extent of the effect of psoriasis on gene expression in the affected
tissue.
Results
We give greater insight into the effects of psoriasis on the up-regulation of some
genes in the cell cycle (CCNB1, CCNA2, CCNE2, CDK1) or the dynamin system (GBPs, MXs,
MFN1), as well as the down-regulation of typical antioxidant genes (catalase, CAT;
superoxide dismutases, SOD1-3; and glutathione reductase, GSR). We also provide a
complete list of the human genes and how they respond in a state of psoriasis.
Conclusion
Our results show that psoriasis affects all chromosomes and many biological functions.
If we further consider the stable and mitotically inheritable character of the psoriasis
phenotype, and the influence of environmental factors, then it seems that psoriasis
has an epigenetic origin. This fit well with the strong hereditary character of the
disease as well as its complex genetic background.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic and PersonalCorporate R&D ProfessionalsOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Dermatological ScienceAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Psoriasis.Annu. Rev. Pathol. 2012; 7: 385-422
- Recent advances in understanding psoriasis.F1000Res. 2016; : 5
- Cytokines in psoriasis.Cytokine. 2015; 73: 342-350
- Psoriasis.Cold Spring Harb. Perspect. Med. 2014; 4 (pii: a015354)
- Pathogenesis and immunotherapy in cutanis psoriasis: what can rheumatologists learn?.Curr. Opin. Rheumatol. 2017; 29: 71-78
- Environmental factors and psoriasis.Curr. Probl. Dermatol. 2007; 35: 118-135
- The skin: an indispensable barrier.Exp. Dermatol. 2008; 17: 1063-1072
- Keratins and the skin.Annu. Rev. Cell. Dev. Biol. 1995; 11: 123-153
- Keratins as the main component for the mechanical integrity of keratinocytes.Proc. Natl. Acad. Sci. U. S. A. 2013; 110: 18513-18518
- Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro.Br. J. Dermatol. 1995; 133: 501-511
- Filaggrin and skin barrier function.Curr. Probl. Dermatol. 2016; 49: 1-7
- Expression of filaggrin-2 protein in the epidermis of human skin diseases: a comparative analysis with filaggrin.Biochem. Biophys. Res. Commun. 2014; 449: 100-106
- The cornified envelope: a model of cell death in the skin.Nat. Rev. Mol. Cell. Biol. 2005; 6: 328-340
- Small proline-rich proteins are cross-bridging proteins in the cornified cell envelopes of stratified squamous epithelia.J. Struct. Biol. 1998; 122: 76-85
- Unique keratinization process in psoriasis: late differentiation markers are abolished because of the premature cell death.J. Dermatol. 2004; 31: 271-276
- Inflammasomes as polyvalent cell death platforms.Cell. Mol. Life. Sci. 2016; 73: 2335-2347
- Interleukin (IL)-1? Is a strong inducer of IL-36? Expression in human colonic myofibroblasts.PLoS One. 2015; 10: e0138423
- The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the ‘fused genes' family.Exp. Dermatol. 2012; 21: 643-649
- Overexpression of psoriasin (S100A7) contributes to dysregulated differentiation in psoriasis.Acta Derm. Venereol. 2017; 97: 441-448
- Chemokines and skin diseases.Arch. Immunol. Ther. Exp. (Warsz). 2015; 63: 109-115
- Up-regulation of Interferon-inducible protein 16 contributes to psoriasis by modulating chemokine production in keratinocytes.Sci. Rep. 2016; 6: 25381
- Kinetics and differential expression of the skin-related chemokines CCL27 and CCL17 in psoriasis, atopic dermatitis and allergic contact dermatitis.Exp. Dermatol. 2011; 20: 789-794
- Association of TAP1 and TAP2 gene polymorphisms with susceptibility to pulmonary tuberculosis.Iran. J. Allergy Asthma Immunol. 2016; 15: 62-68
- Analysis of HLA class II and TAP alleles in Japanese patients with psoriasis vulgaris.Hum. Immunol. 1998; 59: 503-511
- Association of TAP and HLA-DM genes with psoriasis in Koreans.J. Invest. Dermatol. 2003; 120: 616-622
- Human antimicrobial peptides and proteins.Pharmaceuticals (Basel). 2014; 7: 545-594
- The role of antimicrobial peptides in chronic inflammatory skin diseases.Postepy Dermatol. Alergol. 2016; 33: 6-12
- The critical and multifunctional roles of antimicrobial peptides in dermatology.Dermatol. Clin. 2017; 35: 39-50
- The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis.Nat. Commun. 2014; 5: 5621
- Lipocalin-2 and iron trafficking in the tumor microenvironment.Pharmacol. Res. 2017; 120: 146-156
- Increased lipocalin-2 contributes to the pathogenesis of psoriasis by modulating neutrophil chemotaxis and cytokine secretion.J. Invest. Dermatol. 2016; 136: 1418-1428
- The alpha-defensins HNP-1 and HNP-2 are dominant self-peptides presented by HLA class-II molecules in lesional psoriatic skin.Eur. J. Dermatol. 2004; 14: 142-145
- Association of?-defensin copy number and psoriasis in three cohorts of European origin.J. Invest. Dermatol. 2012; 132: 2407-2413
- The mysterious human epidermal cell cycle or an oncogene-induced differentiation checkpoint.ABBV Cell Cycle. 2012; 11: 4507-4516
- The dynamin superfamily: universal membrane tubulation and fission molecules?.Nat. Rev. Mol. Cell Biol. 2004; 5: 133-147
- Interferon-induced mx proteins: dynamin-like GTPases with antiviral activity.Traffic. 2002; 10: 710-717
- Interferon-inducible GTPases in host resistance, inflammation and disease.J. Mol. Biol. 2016; 428: 3495-3513
- Genomic imprinting in mammals.Cold Spring Harb. Perspect. Biol. 2014; 6 (pii: a018382)
- Mx GTPases: dynamin-like antiviral machines of innate immunity.Trends Microbiol. 2015; 23: 154-163
- Mitochondrial fission and fusion.Biochem. Soc. Trans. 2016; 44: 1725-1735
- Entry pathways of herpes simplex virus type 1 into human keratinocytes are dynamin- and cholesterol-dependent.PLoS One. 2011; 10: e25464
- Human papillomavirus type 31 uses a caveolin 1- and dynamin 2-mediated entry pathway for infection of human keratinocytes.J. Virol. 2007; 81: 9922-9931
- Oxidative stress in psoriasis and potential therapeutic use of antioxidants.Free Radic. Res. 2016; 50: 585-595
- Role of enzymatic free radical scavengers in management of oxidative stress in autoimmune disorders.Int. J. Biol. Macromol. 2017; 101: 502-517
- Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation.Breast Cancer Res. Treat. 2012; 134: 71-80
- Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier funcions.Biol. Chem. 2008; 389: 669-680
- Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins.J. Biol. Chem. 2007; 282: 5834-5841
- Involvement of kallikrein-related peptidases in normal and pathologic processes.Dis. Markers. 2015; 946572
- Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin.FASEB J. 2006; 20: 2068-2080
- Kallikrein-related peptidase-8 (KLK8) is an active serine protease in human epidermis and sweat and is involved in a skin barrier proteolytic cascade.J. Biol. Chem. 2011; 286: 687-706
- Kallikrein 5-mediated inflammation in rosacea: clinically relevant correlations with acute and chronic manifestations in rosacea and how individual treatments may provide therapeutic benefit.J. Clin. Aesthet. Dermatol. 2014; 7: 20-25
- An operational definition of epigenètics.Genes. Dev. 2009; 23: 781-783
- Genomic imprinting in mammals.Cold Spring Harb. Perspect. Biol. 2014; 6 (pii: a018382)
- Genomic imprinting in psoriasis and atopic dermatitis: a review.J. Dermatol. Sci. 2015; 80: 89-93
- Epigenetics and psoriasis.J. Eur. Acad. Dermatol. Venereol. 2012; 26: 399-403
- A role for epigenetics in psoriasis: methylated cytosine-guanine sites differentiate lesional from nonlesional skin and from normal skin.J. Invest. Dermatol. 2012; 132: 506-508
- Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris.J. Autoimmun. 2013; 41: 17-24
- Epigenetics in the pathogenesis and pathophysiology of psoriasis vulgaris.J. Drugs Dermatol. 2014; 13: 111-118
- Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis.Clin. Epigenet. 2016; 8: 131
- Epigenetics of psoriatic disease: a systematic review and critical appraisal.J. Autoimmun. 2017; 78: 29-38
Article Info
Publication History
Published online: November 21, 2017
Accepted:
November 18,
2017
Received in revised form:
September 25,
2017
Received:
July 21,
2017
Identification
Copyright
© 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
