11 June 2019 : Laboratory Research
Association of Key Genes and Pathways with Atopic Dermatitis by Bioinformatics Analysis
Jie Zhu1BCDEF, Zheng Wang1EF, Fengzhe Chen1AG*DOI: 10.12659/MSM.916525
Med Sci Monit 2019; 25:4353-4361
Abstract
BACKGROUND: Atopic dermatitis is a chronic inflammatory disease of the skin. It has a high prevalence worldwide and affected persons are prone to recurrent attacks, seriously affecting the physical and mental of patients. The exact etiology of the disease is still unclear.
MATERIAL AND METHODS: There are 7 datasets on atopic dermatitis in the Gene Expression Omnibus database, including 142 lesional and 134 non-lesional skin biopsy samples. Differential analysis was performed after datasets were integrated by robust multi-array average method. Functional modules of GSE99802 were explored by weighted gene co-expression network analysis. The 4 most important modules were enriched into the pathways by Metascape.
RESULTS: Significantly differentially expressed genes included 41 upregulated and 10 downregulated genes. The following 5 of the most important upregulated genes had the strongest association with atopic dermatitis. SERPINB3&4 promote inflammation and impaired skin barrier function in the early stage of atopic dermatitis. S100A9 aggravates the inflammatory response by inducing the activation of toll-like receptor 4, neutrophil chemotaxis, neutrophilic inflammation, and the amplification of interleukin-8. MMP1 is the key protease of skin collagen degradation, keeping the extracellular matrix in dynamic balance. MMP12 induces the aggregation of various inflammatory cells into inflammatory tissue. The enriched pathways of each module mainly include Cellular responses to external stimuli, Metabolism of RNA and Translation, and Infectious disease.
CONCLUSIONS: The associated pathways and genes not only help us understand the molecular mechanism of the disease, but also provide research directions or targets for accurate diagnosis and treatment.
Keywords: Cluster Analysis, Critical Pathways, Dermatitis, Atopic, Genetic Association Studies, Computational Biology, Databases, Genetic, Gene Expression Profiling, Oligonucleotide Array Sequence Analysis, Skin
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