Molecular Mechanisms of Keloid and Hypertrophic Scar Formation

Keloids and hypertrophic scars arise from dysregulated wound healing marked by persistent fibroblast activation and excessive extracellular matrix accumulation. In normal repair, inflammation, proliferation and remodelling phases resolve injury, but in pathological scarring profibrotic signals such as transforming growth factor-β (TGF-β) remain elevated, driving myofibroblast differentiation and unchecked collagen synthesis. Mechanotransduction through integrins and cytoskeletal tension amplifies these cues in regions of high tissue stress, while infiltrating immune cells sustain a cycle of inflammation and fibrosis. At the molecular level, non-coding RNAs—including microRNAs and long non-coding RNAs—fine-tune gene networks governing cell proliferation, apoptosis and matrix remodelling. Epigenetic modifications further shape fibroblast phenotype by altering chromatin accessibility at key profibrotic loci. Together, these interconnected pathways produce the characteristic elevation, rigidity and high recurrence of keloids and hypertrophic scars, underlining the need for targeted therapies that rebalance reparative processes.

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Molecular Mechanisms of Keloid and Hypertrophic Scar Formation publication trend

The graph below shows the total number of articles in molecular mechanisms of keloid and hypertrophic scar formation across all publications each year (not limited to Nature Index journals).

Technical terms

Extracellular matrix (ECM): A network of proteins and polysaccharides that provides structural support and regulates cell behaviour.

Fibroblast: A connective-tissue cell responsible for synthesising collagen and other extracellular matrix components.

Myofibroblast: A specialised fibroblast expressing contractile proteins, driving wound contraction and scar formation.

Transforming growth factor-β (TGF-β): A cytokine that modulates cell proliferation, differentiation and extracellular matrix production.

Non-coding RNA (ncRNA): An RNA molecule not translated into protein, including microRNAs and long non-coding RNAs that regulate gene expression.

Epithelial–mesenchymal transition (EMT): A process by which epithelial cells acquire mesenchymal traits, contributing to fibrosis and tissue remodelling.

References

1. Multimodal roles of transient receptor potential channel activation in inducing pathological tissue scarification. Frontiers in Immunology (2023).
2. Recent Understandings of Biology, Prophylaxis and Treatment Strategies for Hypertrophic Scars and Keloids. International Journal of Molecular Sciences (2018).
3. Current Approaches Targeting the Wound Healing Phases to Attenuate Fibrosis and Scarring. International Journal of Molecular Sciences (2020).
4. Epigenetic modification mechanisms involved in keloid: current status and prospect. Clinical Epigenetics (2020).
5. Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway. Frontiers in Cell and Developmental Biology (2021).