Regulation of Keratinocyte Differentiation by Vitamin D and Its Relationship to Squamous Cell Carcinoma
Vitamin D is a fat-soluble steroid hormone originally described as contributing to the maintenance of normal levels of calcium and phosphorus in the bloodstream. Strictly speaking, it is not a vitamin because human skin can manufacture it, but it is referred to as one for historical reasons. Vitamin D aids in the intestinal absorption of calcium, helping to form and maintain bone mineralization in concert with a number of other vitamins, minerals and hormones. Thus, vitamin D prevents rickets in children and osteomalacia in adults–skeletal diseases that result in defects that weaken bones.
Recent investigations have shown that vitamin D also functions as regulator of cellular growth and differentiation in various tissues, including the skin. The mechanisms by which 1,25 dihydroxyvitamin D3 (1,25(OH)2D3 or calcitriol), the active vitamin D metabolite, alters keratinocyte differentiation are multiple and overlap with the mechanisms by which calcium regulates keratinocyte differentiation. The antiproliferative, prodifferentiating effects of 1,25(OH)2D3 raise the hope that it may prevent malignant transformation of keratinocytes just as it appears to do in many other tissues. In particular, vitamin D has been evaluated for its potential anticancer activity because of the presence of vitamin D receptor (VDR) in most normal and malignant cells including basal and squamous-cell carcinomas and melanomas, and the susceptibility of VDR null mice to develop skin tumors. Physiological and pharmacological actions of 1,25(OH)2D3 in various systems have indicated potential applications of VDR ligands in inflammation, cancer and autoimmune disorders. As such, a better understanding of the metabolism and mechanism of action of vitamin D in the skin has opened up new perspectives for therapeutic application of vitamin D analogs in a number of skin diseases including the prevention of malignancy.
KeywordsStratum Corneum Lamellar Body Keratinocyte Differentiation Epidermal Differentiation Steroid Receptor Coactivator
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