Keloid Pathogenesis and Therapeutic Approaches

Keloids arise from an aberrant wound-healing response in which dermal fibroblasts persist in a hyperproliferative, pro-inflammatory state, depositing excessive extracellular matrix that extends beyond the original injury. Genetic susceptibility, dysregulated transforming growth factor-β signalling, chronic inflammation and local hypoxia jointly fuel fibroblast activation and epithelial-to-mesenchymal transition, while immune cells further sustain a profibrotic niche. Conventional treatments—surgical excision combined with corticosteroid injection or radiotherapy—often yield high recurrence. Emerging strategies seek to intercept key molecular drivers: inhibitors of TGF-β pathways, neutralising antibodies against surface proteins stabilising receptor complexes, mechanotransduction modulators that trigger fibroblast apoptosis, and precision delivery systems for gene silencing or photodynamic therapy. A cohesive understanding of cellular heterogeneity and signalling crosstalk underpins the translation of these targeted approaches into more durable and personalised interventions.

Research from Nature Portfolio

Single-cell transcriptional profiling of keloid tissue has delineated four discrete fibroblast subpopulations, revealing a marked expansion of a mesenchymal subset that drives collagen overproduction. Functional assays have shown that selectively depleting or reprogramming this mesenchymal pool attenuates fibrotic deposition, pointing to subpopulation-specific interventions. These insights into fibroblast heterogeneity establish a robust cellular framework for stratified therapeutic targeting.

Keloid Pathogenesis and Therapeutic Approaches publication trend

The graph below shows the total number of articles in keloid pathogenesis and therapeutic approaches across all publications each year (not limited to Nature Index journals).

Technical terms

Fibroblast heterogeneity: The presence of distinct fibroblast subtypes within keloid tissue that differ in gene expression and fibrotic potential.

Mesenchymal fibroblast: A fibroblast subpopulation characterised by enhanced extracellular matrix production and profibrotic gene expression.

Xenograft model: An animal model created by transplanting human cells or tissues into non-human hosts to study disease mechanisms in vivo.

Mechanotransduction: The process by which cells convert mechanical stimuli, such as ultrasound, into biochemical signals affecting cell behaviour.

Monoclonal antibody: A laboratory-generated antibody designed to bind specifically to a single protein target, used here to inhibit TEM1 function.

References

1. Establishment of a humanized mouse model of keloid diseases following the migration of patient immune cells to the lesion: Patient-derived keloid xenograft (PDKX) model. Experimental & Molecular Medicine (2023).
2. Low‐Frequency Ultrasound Sensitive Piezo1 Channels Regulate Keloid‐Related Characteristics of Fibroblasts. Advanced Science (2024).
3. TEM1/endosialin/CD248 promotes pathologic scarring and TGF-β activity through its receptor stability in dermal fibroblasts. Journal of Biomedical Science (2024).
4. Orthogonal upconversion nanocarriers for combined photodynamic therapy and precisely triggered gene silencing in combating keloids. Journal of Controlled Release (2025).
5. Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases. Nature Communications (2021).
6. The Keloid Disorder: Heterogeneity, Histopathology, Mechanisms and Models. Frontiers in Cell and Developmental Biology (2020).
7. The Roles of Inflammation in Keloid and Hypertrophic Scars. Frontiers in Immunology (2020).