Vitamin D: Molecular Biology and Gene Regulation

Vitamin D produced by sunlight exposure of the skin is essential for mineral metabolism and skeletal health. The high prevalence of vitamin D insufficiency in the normal population and its association with increased risk for osteoporosis, diabetes, hypertension, cardiovascular disorders, tuberculosis, autoimmune disease, and cancer have prompted a comprehensive search for the pathogenic mechanisms underlying these associations. The multitude of actions of the vitamin D system are mediated primarily by the binding of the active vitamin D hormone (1,25(OH)2D3 or calcitriol) to its specific cellular receptor (vitamin D receptor or VDR), which initiates the formation of complex of coregulatory factors that control the rate of gene transcription. The goal of this chapter is to present the current understanding of the molecular mechanisms underlying calcitriol/VDR induction or repression of vitamin D target genes mediating classical and nonclassical vitamin D actions, the abnormalities induced by kidney disease, as well as novel actions of the calcitriol/VDR complex in controlling mRNA translation, and VDR-independent actions of calcitriol regulating cell growth, apoptosis, and survival, with special focus on the pathophysiological significance of these processes in disease prevention in the healthy population and in ameliorating the progression of secondary hyperparathyroidism, renal lesions, renal osteodystrophy, and cardiovascular disorders in patients with kidney disease.