Background Keloid is a pathological skin fibrosis disease characterized by abnormal proliferation of dermal fibroblasts and excessive deposition of extracellular matrix (ECM). Its high recurrence rate necessitates an in-depth investigation of molecular mechanisms to develop effective treatment strategies. Methods In this study, 20 samples of keloid tissue and adjacent normal skin were collected. Transcriptome sequencing and proteome analysis were performed, combined with differential expression analysis, functional enrichment, weighted gene co-expression network analysis (WGCNA), and protein interaction network analysis using the STRING platform, to systematically explore the molecular characteristics of keloid. Results A total of 4,994 genes and 828 proteins were found to be differentially expressed in keloid tissue, with enrichment primarily observed in the PI3K-AKT, TGF-β, ECM-receptor interaction, and mitogen-activated protein kinase (MAPK) signaling pathways. Upregulated hub genes MAGED1, FN1, and COL5A2, as well as downregulated hub genes including IL20RA and CLDN4, were identified by WGCNA. Their respective interaction networks were associated with excessive ECM accumulation and disruption of epidermal structure. Conclusion This study has confirmed that the regulatory network of epidermal dysfunction caused by excessive activation of fibroblasts in keloids through multi-omics integration, which provides a theoretical basis for multi-target therapy targeting ECM remodeling and PI3K-AKT/MAPK pathway.
Lu et al. (Wed,) studied this question.