Screening for key genes associated with atopic dermatitis with DNA microarrays

Abstract

The aim of the present study was to identify key genes associated with atopic dermatitis (AD) using microarray data and bioinformatic analyses. The dataset GSE6012, downloaded from the Gene Expression Omnibus (GEO) database, contains gene expression data from 10 AD skin samples and 10 healthy skin samples. Following data preprocessing, differentially expressed genes (DEGs) were identified using the limma package of the R project. Interaction networks were constructed comprising DEGs that showed a degree of node of >3, >5 and >10, using the Osprey software. Functional enrichment and pathway enrichment analysis of the network comprising all DEGs and of the network comprising DEGs with a high degree of node, were performed with the DAVID and WebGestalt toolkits, respectively. A total of 337 DEGs were identified. The functional enrichment analysis revealed that the list of DEGs was significantly enriched for proteins related to epidermis development (P=2.95E-07), including loricrin (LOR), keratin 17 (KRT17), small proline-rich repeat proteins (SPRRs) and involucrin (IVL). The chemokine signaling pathway was the most significantly enriched pathway (P=0.0490978) in the network of all DEGs and in the network consisting of high degree‑node DEGs (>10), which comprised the genes coding for chemokine receptor 7 (CCR7), chemokine ligand (CCL19), signal transducer and activator of transcription 1 (STAT1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). In conclusion, the list of AD-associated proteins identified in this study, including LOR, KRT17, SPRRs, IVL, CCR7, CCL19, PIK3R1 and STAT1 may prove useful for the development of methods to treat AD. From these proteins, PIK3R1 and KRT17 are novel and promising targets for AD therapy.

From the morphological to the transcriptomic characterization of a compromised three-dimensional in vitro model mimicking atopic dermatitis

“…This explains why, up to the present time, only clinical studies have investigated the transcriptome of AD skin . Similarly to the difference observed between patients with AD and healthy subjects, our transcriptomic analysis revealed a clear difference in the expression of 26 genes between compromised and normal RE models, including key markers of AD . Genes that are differentially regulated between the compromised RE and AD skin are listed in Table S3 (see Supporting Information).…”

“…Expression levels are shown in red (high) and green (low). (b) List of the 26 genes regulated in a similar manner between atopic dermatitis ( AD ) and our compromised RE . +, overexpressed genes; −, underexpressed genes; bold, key markers of AD .…”

“…59,60 Similarly to the difference observed between patients with AD and healthy subjects, our transcriptomic analysis revealed a clear difference in the expression of 26 genes between compromised and normal RE models, including key markers of AD. 51,59,[61][62][63][64][65][66][67][68] Genes that are differentially regulated between the compromised RE and AD skin are listed in Table S3 (see Supporting Information). A recent genome-wide association study has identified a total of 19 loci associated with AD in vivo, gathering seven biological processes.…”

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

“…Transcriptomic studies on atopic dermatitis have been focusing on the concept of a dysregulated, e.g., Th2-like, immune response [91], and the role of cutaneous barrier abnormalities [92]. In this respect, the dysregulated key epidermal genes filaggrin (FLG) and loricrin (LOR) were grouped as members of the epidermal differentiation complex (EDC) [90,93,94], which is encoded on the 1q21 susceptibility locus [95]. Factors of the EDC are often antimicrobial effector molecules of the innate immune response [96].…”

Identification of Hub Genes and Key Pathways Associated with Atopic Dermatitis via Integrated Bioinformatics

“…The top 50 target proteins in each mentioned algorism had been integrated for key hub genes. The 23 VDR (degree value: 19), KIT (24), BCL2L11 (16), NFKBIA (22), KRAS (30), IL13 (37), JAK2 (35), STAT3…”