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Updated: Oct 26, 2026
In Vitro Model of Human Cutaneous Hypertrophic Scarring using Macromolecular Crowding
Published on: May 1, 2020
Comparative Transcriptomic Signatures of Keloids and Hypertrophic Scars: A Genetic Association Pilot Study
Luiz Fernando Lima Barros1, Andre L F Faustino2, Ândrea Ribeiro-Dos-Santos3
1From Department of Medicine, University of São Paulo, São Paulo, Brazil.
Background:
Keloids and hypertrophic scars are fibroproliferative skin disorders with overlapping clinical features but distinct biological behaviors, posing major therapeutic challenges in plastic and reconstructive surgery. Understanding their molecular mechanisms is critical for developing targeted interventions.
Methods:
A comparative study of transcriptomic profiles of keloid (n = 3) and hypertrophic scar (n = 3) lesions from female patients (thoracic region, no comorbidities). RNA-seq was performed, and differential gene expression was analyzed using DESeq2. Functional enrichment analyses were conducted via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, stratifying upregulated and downregulated genes.
Results:
Keloids exhibited upregulation of genes involved in ribosome biogenesis, RNA splicing, chromosomal organization, and cell cycle progression (eg, USP39, CEP85, RNF180, VHL), reflecting a sustained anabolic and proliferative state. In contrast, hypertrophic scars were enriched in immune and metabolic pathways, with higher expression of ICAM1, MRC1/CD206, PDE2A, TMEM120A, and TMEM135, suggesting modulation by inflammatory cytokines (interleukin-6, transforming growth factor beta) and M2 macrophage polarization. Integrated Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses highlighted central pathways including transforming growth factor beta, nuclear factor κB, advanced glycation end products-receptor for advanced glycation end products, and cAMP response element-binding protein, with polycomb repressive complex activation identified as a shared yet differentially regulated epigenetic axis.
Conclusions:
This study revealed distinct molecular signatures in keloid and hypertrophic scars, elucidating divergent mechanisms of fibroblast proliferation, inflammation, and tissue remodeling. These findings provide a mechanistic framework for translational strategies in plastic surgery, including precision-targeted therapies, drug repurposing, and gene-based interventions, advancing management of pathological skin fibrosis and improving surgical outcomes.