Expression of CYP24A1 protein in keloids and normal skin samples. Immunohistochemistry was used to localize CYP24A1 in sections of keloids (a–c) and normal skin (g–i). Negative controls were processed identically but without primary antibody (d–f for keloid samples; j–l for normal skin samples). Levels of CYP24A1 were variable among samples within each group, keloid or normal skin, but staining levels were higher overall in the keloid samples; Representative sections illustrating this variability are shown. Keloid samples from donors 843K (a, d), 934K (b, e), and 991K (c, f) are shown, as are normal skin samples from donors 880 (g, j), 886 (h, k) and 974 (i,l); see Table 1 for donor demographic information. The scale bar in panel l (0.1 mm) is the same for all images. Credit: Burns & Trauma (2025). DOI: 10.1093/burnst/tkae063
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, the study delves deeper into the molecular drivers of keloid pathology, identifying potential targets for more effective interventions.
A study published in Burns & Trauma has shed light on how inhibiting CYP24A1, an enzyme involved in vitamin D metabolism, affects keloid keratinocytes. Conducted by researchers at the University of Cincinnati, the investigation revealed that suppressing CYP24A1 could reduce the expression of profibrotic genes, offering a fresh perspective on keloid treatment strategies.
The study employed an innovative approach, isolating primary keratinocytes from normal and keloid skin samples. By culturing these cells with and without vitamin D, alongside inhibitors such as ketoconazole and VID400, the researchers assessed their impact on gene expression and cell behavior. Their findings were striking: 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. Furthermore, 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.
Production of vitamin D in the skin. Vitamin D3 (D3) is synthesized in keratinocytes from the precursor 7-dehydrocholesterol in response to ultraviolet radiation in sunlight. D3 is metabolized to 25-hydroxy vitamin D (25(OH)D), the form most commonly measured in the blood as a marker of vitamin D status, by CYP27A1. 25(OH)D is metabolized to 1,25-dihydroxyvitamin D (1,25(OH)2D), the hormonally active form of vitamin D, by CYP27B1. The enzyme CYP24A1 inactivates both 25(OH)D and 1,25(OH)2D. Transcription of the gene encoding CYP24A1 is induced by 1,25(OH)2D, which serves as a feedback loop to modulate levels of active vitamin D. The inhibitors ketoconazole and VID400 block the activity of CYP24A1, which may lead to decreased profibrotic gene expression by decreasing inactivation of 1,25(OH)2D.Credit: Burns & Trauma (2025). DOI: 10.1093/burnst/tkae063
Dr. Dorothy M Supp, senior author of the study, said “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. 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.
More information:
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
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Citation: Vitamin D and keloid scars: Researchers find inhibiting enzyme could lead to treatment (2025, January 22) retrieved 23 January 2025 from
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