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Whole Transcriptome Profiling of Lesional Psoriatic and Adjacent Normal Skin Tissues

ABSTRACT: Purpose: To identify the differentially expressed genes in lesional skin of psoriasis patients compared to adjacent normal skin tissue by Next Generation Sequencing. Methods: Total RNA was isolated from 24 paired lesional and adjacent normal skin tissue samples and Next Generation Sequencing was performed. The sequences reads were trimmed of adapter sequences and quality trimmed using CutAdapt, followed by alignment to the human genome (hg19/GRCh37) by 'STAR (v2.7.10a)'. The aligned files were sorted based on chromosomal location. Trancript assembly was performed using StringTie (v1.3.3b) and python script prepDE.py was used to obtain the raw read counts for all annotated genes. Differnetial expression analysis was performed with the raw reads using R-package 'edgeR'. Gene ontology with the deregulated genes was performed uign DAVID GO. The differentially expressed genes were integrated with differentially expressed miRNAs (GSE183547) and differentially methylated CpGs (GSE115797) to identify the genes regulated by miRNA and DNA metylation respectively. Results: We identified 1,541 differentially expressed protein-coding genes with at least 2-fold deregulation that were statistically significant (FDR ≤ 0.05). The deregulated genes were found to be associated with biological processes including inflammatory response, cytokine mediated signaling, keratinization, neutrophil chemotaxis and defense response to virus among the top enriched processes. Inetgrative analysis with small RNA-seq and DNA methylation profiling using Illumina Infinum 450K BeadArray identified 487 and 321 genes to be regulated by miRNA and DNA methylation respectively. Conclusions: Our multi-omics integrative analysis identfied the biological processes regulated exclusively as well as combinatorially by miRNAs and DNA methylation in the disease pathogenesis of psoriasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244679 | GEO | 2026/03/12

REPOSITORIES: GEO

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Project description:Background: Plaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available. Aim: The aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease. Methods: Skin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients' skin compared to skin of the healthy volunteers. Results: The performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. We discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG in normally looking skin of the patients. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes. Conclusion: Our findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease.

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Whole Transcriptome Profiling of Lesional Psoriatic and Adjacent Normal Skin Tissues

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