INTRODUCTION
Vitamin D is a bioactive nutrient which can be obtained from the diet or synthesized in the skin from 7-dehydrocholesterol following exposure to UVB light.1 Newly formed pre-vitamin D3 is converted to vitamin D3. Due to a higher concentration of melanin inhibiting UVB light, individuals with darkly pigmented skin have reduced vitamin D synthesis and are at increased risk for vitamin D deficiency.1 In the liver, the 25-hydroxylase enzyme converts vitamin D3 into the prohormone 25-hydroxyvitamin D (25(OH)D), the biomarker of vitamin D status. Lower serum 25(OH)D levels have been associated with a variety of dermatologic conditions, such as atopic dermatitis,2 psoriasis,3 and systemic lupus erythematosus.4 In the kidney, 25(OH)D is converted into its biologically active form 1,25-dihydroxyvitamin D (1,25(OH)2D) (also known as calcitriol) by 1-α-hydroxylase. Topical formulations of vitamin D analogs (calcipotriol and tacalcitol) have been proven effective for the treatment of plaque psoriasis.5,6
Through the vitamin D receptor (VDR), vitamin D is able to regulate genes containing vitamin D response elements (VDREs).7 Various immune cells (T cells, B cells, natural killer (NK) cells, and monocytes) contain the VDR, so vitamin D is thought to regulate their function.8 Inflammation is a critical step in wound healing, but can cause problems if prolonged or excessive. Researchers have shown that vitamin D inhibits pro-inflammatory cytokine production (Interleukin (IL)-6, IL-8, IL-17, IL-21, and interferon (IFN)-γ)9,10 while increasing anti-inflammatory cytokines (IL-10)11,12 in immune cells, epidermal cells, and fibroblast cell culture studies.
Following inflammation, the proliferative phase of wound healing proceeds and fibroblasts, keratinocytes, and endothelial cells aid in the formation of new tissue from collagen and other extracellular matrix (ECM) molecules.13 Cathelicidin (LL-37), a human antimicrobial peptide, has a variety of roles in wound healing and is known to be upregulated by vitamin D.14,15 In human dermal fibroblasts, cathelicidin inhibits collagen synthesis.16 Cathelicidin has also been shown to activate the migration of human keratinocytes in vitro and increase the rate of re-epithelialization and granulation tissue formation in diabetic wounds in vivo.17 More directly, VDR knockout mice display impaired epidermal stem cell migration, differentiation, and proliferation.18
Although scarring is a normal component of wound healing, sometimes an overgrowth of scar tissue occurs leading to the formation of hypertrophic scars or keloid scars. Unlike hypertrophic scars, keloids extend beyond the site of the original injury and involve adjacent normal skin.19 Keloids are more common in individuals with darker skin and can be painful, itchy, and cause hyperesthesia.20 In black patients with keloids, inflammatory signaling molecules such as serum IL-6, tumor necrosis factor (TNF)-α, and IFN-β were shown to be elevated in comparison to control subjects.21 Numerous in vitro
Through the vitamin D receptor (VDR), vitamin D is able to regulate genes containing vitamin D response elements (VDREs).7 Various immune cells (T cells, B cells, natural killer (NK) cells, and monocytes) contain the VDR, so vitamin D is thought to regulate their function.8 Inflammation is a critical step in wound healing, but can cause problems if prolonged or excessive. Researchers have shown that vitamin D inhibits pro-inflammatory cytokine production (Interleukin (IL)-6, IL-8, IL-17, IL-21, and interferon (IFN)-γ)9,10 while increasing anti-inflammatory cytokines (IL-10)11,12 in immune cells, epidermal cells, and fibroblast cell culture studies.
Following inflammation, the proliferative phase of wound healing proceeds and fibroblasts, keratinocytes, and endothelial cells aid in the formation of new tissue from collagen and other extracellular matrix (ECM) molecules.13 Cathelicidin (LL-37), a human antimicrobial peptide, has a variety of roles in wound healing and is known to be upregulated by vitamin D.14,15 In human dermal fibroblasts, cathelicidin inhibits collagen synthesis.16 Cathelicidin has also been shown to activate the migration of human keratinocytes in vitro and increase the rate of re-epithelialization and granulation tissue formation in diabetic wounds in vivo.17 More directly, VDR knockout mice display impaired epidermal stem cell migration, differentiation, and proliferation.18
Although scarring is a normal component of wound healing, sometimes an overgrowth of scar tissue occurs leading to the formation of hypertrophic scars or keloid scars. Unlike hypertrophic scars, keloids extend beyond the site of the original injury and involve adjacent normal skin.19 Keloids are more common in individuals with darker skin and can be painful, itchy, and cause hyperesthesia.20 In black patients with keloids, inflammatory signaling molecules such as serum IL-6, tumor necrosis factor (TNF)-α, and IFN-β were shown to be elevated in comparison to control subjects.21 Numerous in vitro
