Abstract
BackgroundThe skin is the largest organ of the body and has multiple functions. Wounds remain a significant healthcare problem due to the large number of traumatic and pathophysiological conditions patients suffer.MethodsGene expression profiles of 37 biopsies collected from patients undergoing split-thickness skin grafts at five different time points were downloaded from two datasets (GSE28914 and GSE50425) in the Gene Expression Omnibus (GEO) database. Principal component analysis (PCA) was applied to classify samples into different phases. Subsequently, differentially expressed genes (DEGs) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment analyses were performed, and protein–protein interaction (PPI) networks created for each phase. Furthermore, based on the results of the PPI, hub genes in each phase were identified by molecular complex detection combined with the ClueGO algorithm.ResultsUsing principal component analysis, the collected samples were divided into four phases, namely intact phase, acute wound phase, inflammatory and proliferation phase, and remodeling phase. Intact samples were used as control group. In the acute wound phase, a total of 1 upregulated and 100 downregulated DEGs were identified. Tyrosinase (TYR), tyrosinase Related Protein 1 (TYRP1) and dopachrome tautomerase (DCT) were considered as hub genes and enriched in tyrosine metabolism which dominate the process of melanogenesis. In the inflammatory and proliferation phase, a total of 85 upregulated and 164 downregulated DEGs were identified. CHEK1, CCNB1 and CDK1 were considered as hub genes and enriched in cell cycle and P53 signaling pathway. In the remodeling phase, a total of 121 upregulated and 49 downregulated DEGs were identified. COL4A1, COL4A2, and COL6A1 were considered as hub genes and enriched in protein digestion and absorption, and ECM-receptor interaction.ConclusionThis comprehensive bioinformatic re-analysis of GEO data provides new insights into the molecular pathogenesis of wound healing and the potential identification of therapeutic targets for the treatment of wounds.
Highlights
The skin is the largest organ of the body and has multiple functions
Partial-thickness skin grafts create a superficial wound at the donor site [3], characterized by a standardized depth of injury that extends to the epidermis and papillary dermis, which are renowned for their prolonged duration of healing, often resulting in a scar [4, 5]
The results demonstrated that following normalization, the median of the different samples was almost the same value, indicating a high degree of standardization (Additional file 1A and B)
Summary
The skin is the largest organ of the body and has multiple functions. Wounds remain a significant healthcare problem due to the large number of traumatic and pathophysiological conditions patients suffer. Partial-thickness skin grafts create a superficial wound at the donor site [3], characterized by a standardized depth of injury that extends to the epidermis and papillary dermis, which are renowned for their prolonged duration of healing, often resulting in a scar [4, 5]. Microarray and high-throughput sequencing technologies provide genome-wide profiling of gene expression, allowing researchers to study WH in both animal models and humans. It provides a large choice of gene sets with data representing the differential stages of normal WH [7]. As bioinformatic technology rapidly advances, numerous data profiles from the GEO database have been reanalyzed by researchers
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