From The British Journal of Dermatology
Vitamin D: A Novel Therapeutic Approach for Keloid, an in vitro Analysis
G.Y. Zhang; T. Cheng; Q. Luan; T. Liao; C.L. Nie; X. Zheng; X.G. Xie; W.Y. Gao
Keloids are distinguished by substantial deposition of collagen in the dermis, resulting in an imbalanced production and aggregation of extracellular matrix (ECM). The precise molecular and biochemical dysfunctions are still unknown, but tissue fibrosis after injury is known to be a reactive process, in which several different factors modulate the relevant pathways.[1,2] Data reported with respect to differences between keloid fibroblasts and normal skin fibroblasts in the context of cellular functions such as collagen production, degradation, and expression and activity of collagenases, have been diverse. Collagen synthesis and degradation, including collagenase activity, are known to be significantly higher in keloid tissues.[3–5]
Vitamin D, specifically its most active metabolite 1,25-dihydroxyvitamin D3 (1,25D), or calcitriol, plays an important role in a variety of biological processes such as calcium homeostasis, hormone secretion, cell proliferation and differentiation.[6–9] Most, if not all, pleiotropic actions of vitamin D and its analogues are mediated by the specific vitamin D receptor (VDR), a ligand-dependent transcription factor that belongs to the steroid nuclear receptor gene family.[6,10] Vitamin D has been shown to inhibit collagen synthesis in interstitial fibrosis and in the rat glomerulonephritis model and heart fibrosis, by inhibiting the production and accumulation of interstitial matrix components or suppressing transforming growth factor (TGF)-β1 gene expression.[7,11,12] Furthermore, it has been found that in NIH/3T3 fibroblastic cells and primary lung fibroblasts, the expressed functional VDRs and vitamin D opposed the effects of TGF-β1, a well-studied profibrotic factor in these cells. Moreover, several studies have demonstrated the effectiveness of orally administered 1,25-dihydroxycholecalciferol (calcitriol), the biologically active form of vitamin D, as a treatment for scleroderma, a skin fibrosis disease.[14–16] However, relatively little is known about the potential role of vitamin D in this dermal fibrosis formation.
Based on the above studies, we postulated that vitamin D may function as a countervailing influence to attenuate collagen formation during keloid pathogenesis, and that unregulated collagen expression in keloid fibroblasts both at baseline and after TGF-β1 stimulation induced by vitamin D might be one of the mechanisms by which this occurs. To test this hypothesis, we examined the effects of vitamin D on keloid fibroblasts and TGF-β1-induced collagen expression in the present study.