Keloids are fibrotic scars that extend beyond the boundaries of the original wound, often causing physical disfigurement and emotional distress. These scars are driven by an overproduction of extracellular matrix components like type I collagen, linked to an imbalance in tissue repair mechanisms.
Current treatments show limited efficacy due to an incomplete understanding of the molecular processes behind keloid formation, leaving patients with few reliable options. Addressing this gap, a recent study published in Burns & Trauma has delved deeper into the molecular drivers of keloid pathology, identifying potential targets for more effective interventions.
The study, conducted by researchers at the University of Cincinnati, focused on inhibiting CYP24A1, an enzyme involved in vitamin D metabolism, to assess its impact on keloid keratinocytes. The investigation revealed that suppressing CYP24A1 could reduce the expression of profibrotic genes, offering a new perspective on keloid treatment strategies.
By isolating primary keratinocytes from normal and keloid skin samples and culturing them with and without vitamin D, alongside inhibitors such as ketoconazole and VID400, the researchers were able to assess their impact on gene expression and cell behavior. Results showed that CYP24A1 was significantly overexpressed in keloid keratinocytes at both mRNA and protein levels.
While ketoconazole broadly reduced cell proliferation, VID400 specifically targeted the growth of keloid keratinocytes without affecting migration. Additionally, both inhibitors effectively suppressed the expression of profibrotic genes, such as periostin and hyaluronan synthase 2. When combined with vitamin D, these inhibitors amplified gene-specific effects, suggesting their potential as adjunct therapies for keloids.
Dr. Dorothy M Supp, senior author of the study, commented on the significance of the findings, stating that “The identification of CYP24A1 as a key factor in keloid keratinocytes marks a transformative moment in dermatology. This study provides a deeper understanding of the molecular mechanisms driving keloid formation and opens the door to targeted therapies. By modulating the activity of CYP24A1, we may improve treatment efficacy and address the recurrence challenges that patients face. This innovative work lays the groundwork for a new era in keloid management.”
The implications of these findings extend beyond immediate clinical applications. By spotlighting CYP24A1 as a critical player in keloid pathology, the research signals a shift from reactive treatment strategies to proactive prevention of keloid formation.
In conclusion, the study published in Burns & Trauma sheds light on a promising avenue for keloid treatment by targeting CYP24A1 and its role in keloid keratinocytes. The research opens up new possibilities for more effective therapies and a proactive approach to managing keloid scars.
Reference:
Jennifer M Hahn et al, CYP24A1 is overexpressed in keloid keratinocytes and its inhibition alters profibrotic gene expression, Burns & Trauma (2025). DOI: 10.1093/burnst/tkae063.
