Researchers in Japan have identified a protein that may be involved in the development and persistence of keloid scars – overgrown, raised scars that extend beyond the site of skin injury. The study, published in The Journal of Pathology, reports that PIEZO2 is present at higher levels in the scar-forming cells of keloid tissue, and that this may contribute to their aggressive growth and resistance to healing.
Keloid scars are a type of abnormal wound healing that can appear after burns, cuts, or other skin injuries. Unlike typical scars, keloids can continue to grow over time and often cause cosmetic or functional problems. The underlying mechanisms behind keloid formation remain unclear, and treatments are often only partially effective.
The researchers compared resected keloid specimens with lymphedema controls and assessed bulk RNA expression across thirty cases meeting predefined clinical criteria. Single-cell RNA sequencing characterized the cellular distribution of mechanoreceptor expression. Fibroblasts and endothelial cells accounted for most PIEZO2 signal, whereas PIEZO1 was broadly expressed across cell types and did not distinguish disease groups or recurrence status.
Within fibroblasts, PIEZO2 expression was largely confined to a subset with higher expression of collagen genes, including COL1A1, COL1A2, COL3A1, and COL6A2, and with enrichment of gene ontology categories related to extracellular matrix structure and organization.
Confocal microscopy showed clustering of PIEZO2-positive cells around vascular and lymphatic structures, and transmission electron microscopy demonstrated dense core granules in interstitial cells near lymphatic vessels. These features were more prominent in histologically active keloid regions than in inactive centers.
Recurrence analysis showed a higher short-term recurrence frequency in the PIEZO2 higher-expression group, while PIEZO1 expression did not separate outcomes.
Sample size, demographic homogeneity, and the absence of direct mechanostimulation assays were noted as study limitations.
Newsletters
Receive the latest pathologist news, personalities, education, and career development – weekly to your inbox.
