Identification of Molecular Signatures in Mild Intrinsic Atopic Dermatitis by Bioinformatics Analysis
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Background: Atopic dermatitis (AD) is recognized as a common inflammatory skin disease and frequently occurred in Asian and Black individuals. Objective: Since the limitation of dataset associated with human severe AD, this study aimed to screen potential novel biomarkers involved in mild AD. Methods: Expression profile data (GSE75890) were obtained from the database of Gene Expression Omnibus. Using limma package, the differentially expressed genes (DEGs) between samples from AD and healthy control were selected. Furthermore, function analysis was conducted. Meanwhile, the protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-target regulatory network were constructed. And quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expressions patterns of key genes. Results: In total, 285 DEGs including 214 upregulated and 71 downregulated genes were identified between samples from two groups. The upregulated DEGs were mainly involved in nine pathways, such as hematopoietic cell lineage, pertussis, p53 signaling pathway, staphylococcus aureus infection, and cell cycle, while tight junction was the only pathway enriched by the downregulated DEGs. Cyclin B (CCNB)1, CCNB2, cyclin A (CCNA)2, C-X-C motif chemokine ligand (CXCL)10, and CXCL9 were key nodes in PPI network. The TF-miRNA-target gene regulatory network focused on miRNAs such as miR-106b, miR-106a, and miR-17, TFs such as nuclear factor kappa B subunit 1, RELA proto-oncogene, Sp1 transcription factor, and genes such as matrix metallopeptidase 9, peroxisome proliferator activated receptor gamma , and serpin family E member 1. Moreover, the upregulation of these genes, including CCNB1, CCNB2, CCNA2, CXCL10, and CXCL9 were confirmed by qRT-PCR. Conclusion: CCNB1, CCNB2, CCNA2, and CXCL9 might be novel markers of mild AD. miR-106b and miR-17 may involve in regulation of immune response in AD patients.
Abstract
Background: Atopic dermatitis (AD) is recognized as a common inflammatory skin disease and frequently occurred in Asian and Black individuals. Objective: Since the limitation of dataset associated with human severe AD, this study aimed to screen potential novel biomarkers involved in mild AD. Methods: Expression profile data (GSE75890) were obtained from the database of Gene Expression Omnibus. Using limma package, the differentially expressed genes (DEGs) between samples from AD and healthy control were selected. Furthermore, function analysis was conducted. Meanwhile, the protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-target regulatory network were constructed. And quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expressions patterns of key genes. Results: In total, 285 DEGs including 214 upregulated and 71 downregulated genes were identified between samples from two groups. The upregulated DEGs were mainly involved in nine pathways, such as hematopoietic cell lineage, pertussis, p53 signaling pathway, staphylococcus aureus infection, and cell cycle, while tight junction was the only pathway enriched by the downregulated DEGs. Cyclin B (CCNB)1, CCNB2, cyclin A (CCNA)2, C-X-C motif chemokine ligand (CXCL)10, and CXCL9 were key nodes in PPI network. The TF-miRNA-target gene regulatory network focused on miRNAs such as miR-106b, miR-106a, and miR-17, TFs such as nuclear factor kappa B subunit 1, RELA proto-oncogene, Sp1 transcription factor, and genes such as matrix metallopeptidase 9, peroxisome proliferator activated receptor gamma , and serpin family E member 1. Moreover, the upregulation of these genes, including CCNB1, CCNB2, CCNA2, CXCL10, and CXCL9 were confirmed by qRT-PCR. Conclusion: CCNB1, CCNB2, CCNA2, and CXCL9 might be novel markers of mild AD. miR-106b and miR-17 may involve in regulation of immune response in AD patients.
참고문헌 (35)
- Hua T, "Atopic dermatitis in US adults: epidemiology, association with marital status, and atopy", Ann Allergy Asthma Immunol, 121, pp.622~624 (2018)
- Sacotte R, "Epidemiology of adult atopic dermatitis", Clin Dermatol, 36, pp.595~605 (2018)
- Kaufman BP, "Atopic dermatitis in diverse racial and ethnic groups-Variations in epidemiology, genetics, clinical presentation and treatment", Exp Dermatol, 27, pp.340~357 (2018)
- Rahman S, "The pathology and immunology of atopic dermatitis", Inflamm Allergy Drug Targets, 10, pp.486~496 (2011)
- Pavel AB, "Oral Janus kinase", SYK inhibition(ASN002)suppresses inflammation and improves epidermal barrier markers in patients with atopic dermatitis, 2019, pp.144, 1011~1024
- Guttman-Yassky E, "Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis", J Allergy Clin Immunol, 143, pp.155~172 (2019)
- Beck LA, "Dupilumab treatment in adults with moderate-to-severe atopic dermatitis", N Engl J Med, 371, pp.130~139 (2014)
- Lee HJ, "Atopic march from atopic dermatitis to asthma-like lesions in NC", Nga mice is accelerated or aggravated by neutralization of stratum corneum but partially inhibited by acidification, 2015, pp.135, 3025~3033
- Sonkoly E, "MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4", J Allergy Clin Immunol, 126, pp.581~589 (2010)
- Martel BC, "Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis", Exp Dermatol, 25, pp.453~459 (2016)
- Carvalho BS, "A framework for oligonucleotide microarray preprocessing", Bioinformatics, 26, pp.2363~2367 (2010)
- Bolstad BM, "A comparison of normalization methods for high density oligonucleotide array data based on variance and bias", Bioinformatics, 19, pp.185~193 (2003)
- Irizarry RA, "Exploration, normalization, and summaries of high density oligonucleotide array probe level data", Biostatistics, 4, pp.249~264 (2003)
- Smyth GK, "Bioinformatics and computational biology solutions using R and bioconductor", pp.397~420 (2005), Springer-Verlag
- Huang da W, "Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources", Nat Protoc, 4, pp.44~57 (2009)
- Kanehisa M, "KEGG : Kyoto encyclopedia of genes and genomes", Nucleic Acids Res, 28, pp.27~30 (2000)
- Szklarczyk D, "STRING v10: protein-protein interaction networks, integrated over the tree of life", Nucleic Acids Res, 43(Database issue), pp.D447~D452 (2015)
- Shannon P, "Cytoscape : a software environment for integrated models of biomolecular interaction networks", Genome Res, 13, pp.2498~2504 (2003)
- Bandettini WP, "MultiContrast Delayed Enhancement(MCODE)improves detection of subendocardial myocardial infarction by late gadolinium enhancement cardiovascular magnetic resonance : a clinical validation study", J Cardiovasc Magn Reson, 14, pp.83~ (2012)
- Dweep H, "miRWalk--database : prediction of possible miRNA binding sites by"walking"the genes of three genomes", J Biomed Inform, 44, pp.839~847 (2011)
- Han H, "TRRUST v2 : an expanded reference database of human and mouse transcriptional regulatory interactions", Nucleic Acids Res, 46, pp.D380~D386 (2018)
- Boguniewicz M, "Atopic dermatitis : a disease of altered skin barrier and immune dysregulation", Immunol Rev, 242, pp.233~246 (2011)
- Akdis M, "T helper(Th)2 predominance in atopic diseases is due to preferential apoptosis of circulating memory", effector Th1 cells, 2003, pp.17, 1026~1035
- Grewe M, "A role for Th1and Th2 cells in the immunopathogenesis of atopic dermatitis", Immunol Today, 19, pp.359~361 (1998)
- Shimada Y, "Both Th2 and Th1 chemokines (TARC", CCL17, MDC, CXCL9) are elevated in sera from patients with atopic dermatitis, pp.J Dermatol Sci, 2004[DOI]
- Abramo F, "Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis", BMC Vet Res, 10, pp.21~ (2014)
- Meng K, "The effects of vitamin K1 and vitamin K2 on the proliferation, cytokine production and regulatory T-cell frequency in peripheral blood mononuclear cells of paediatric atopic dermatitis patients", Exp Dermatol, 27, pp.1058~1060 (2018)
- Rożalski M, "MiRNA in atopic dermatitis", Postepy Dermatol Alergol, 33, pp.157~162 (2016)
- Lv Y, "Profiling of serum and urinary microRNAs in children with atopic dermatitis", PLoS One, 9, pp.e115448~ (2014)
- Björkqvist J, "Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III", J Clin Invest, 125, pp.3132~3146 (2015)
- Nguyen GN, "Duplication and loss of function of genes encoding RNA polymerase III subunit C4 causes hybrid incompatibility in rice", G3(Bethesda), 7, pp.2565~2575 (2017)
- Huang L, "KPNA2 promotes migration and invasion in epithelial ovarian cancer cells by inducing epithelial-mesenchymal transition via Akt", GSK-3β, J Cancer, pp.2018, 9[DOI]
- Yamada K, "Cell surface localization of importin α1", KPNA2 affects cancer cell proliferation by regulating FGF1 signalling, 2016, pp.6, 21410~
- Sun G, "Decreased MiR-17 in glioma cells increased cell viability and migration by increasing the expression of Cyclin D1, p-Akt and Akt", PLoS One, 13, pp.e0190515~ (2018)
- Lancaster GI, "The dual-specificity phosphatase 2(DUSP2)does not regulate obesity-associated inflammation or insulin resistance in mice", PLoS One, 9, pp.e111524~ (2014)