1290 Despite abnormal vitamin D receptor expression in keloid scars, keloid keratinocytes can respond to vitamin D treatment in vitro

Abstract

Keloids are fibroproliferative scars that are more prevalent in populations with darkly pigmented skin, such as African Americans. The basis for increased keloid susceptibility in skin of color is not known. Vitamin D is produced in skin in response to UV light, and rates of vitamin D deficiency are higher in populations with darker skin. Vitamin D, through binding of the vitamin D receptor (VDR), regulates calcium homeostasis, cell proliferation, differentiation, inflammation, and fibrosis. Hypothetically, the link between pigmentation and keloid formation may involve vitamin D signaling. Because ligand-bound VDR acts as a transcription factor, ligand-dependent target gene regulation requires nuclear localization. VDR expression and nuclear localization were analyzed in keloid scars (N=24) and normal skin (N=24). Immunohistochemistry demonstrated reduced VDR levels in most keloids, and the percentage of epidermal nuclei positive for VDR was significantly lower in keloids vs. normal skin. Keloid scars of black (N=18) or white (N=6) donors showed significantly reduced VDR nuclear localization vs. normal epidermis of black (N=12) or white (N=12) donors, respectively. Further, among normal samples, VDR nuclear localization was significantly lower in epidermis of black vs. white donors. To determine if keloid cells are competent to respond to vitamin D stimulation, keratinocytes were isolated from keloid scars and normal skin samples (N=4 each). VDR mRNA expression levels were similar in keloid and normal keratinocytes in vitro, and treatment with 100 nM calcitriol significantly increased expression of the vitamin D target genes Cathelicidin and CYP24A1 in both groups. The results suggest that VDR is involved in keloid pathology and hint at a possible role for VDR in the increased susceptibility to keloid scarring in individuals with darkly pigmented skin. Further, because keloid keratinocytes can respond to vitamin D treatment by appropriate upregulation of target genes, the results suggest a potential therapeutic role for vitamin D in prevention or treatment of keloids.