Vitamin D Receptor in Human Health and Disease—2nd Edition

Dear Colleagues,

Vitamin D is a seco-steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in the mineralization of bone. In addition to its endocrine effects, vitamin D plays important autocrine/paracrine roles. The last step in the activation of vitamin D, the hydroxylation on carbon 1, mainly occurs in the kidney. However, extrarenal sites showing 1 alpha-hydroxylase activity have also been found. The hormonally active form of vitamin D (1,25(OH)2D3 or calcitriol) mediates its biological effects by binding to the vitamin D receptor, which then translocates to the nucleus of the cell and binds to specific DNA sites to modify the expression of target genes. After activation of the receptor, the protein changes its tridimensional conformation; this change is the key process to mediate its nuclear actions. Several steps take place to increase or decrease the transcription rate of a target gene. First, homodimerization of the vitamin D receptor or heterodimerization with the retinoid X receptor allows the complex to enter the nucleus and bind to DNA. Then, several proteins are recruited to the complex that either increase or decrease chromatin condensation, thus acting like co-repressors or co-activators, respectively, finally decreasing or increasing the target gene transcription. The co-activators bind several extra proteins that build a bridge to the basal transcription machinery.

In recent decades, a number of basic and clinical studies have pointed to the important role that vitamin D plays in various physiological and pathological processes throughout the body. Thus, it has been shown that vitamin D exerts its pleiotropic effects in a variety of target cells, where it is involved in a wide array of new functions that are unrelated to its actions on mineral metabolism. For instance, vitamin D has been involved in the regulation of vascular smooth muscle cell proliferation and calcification, in the modulation of the renin–angiotensin system and, in general, in cardiovascular health. Furthermore, Vitamin D negatively regulates the growth of breast, prostate, and colon cancer cells. It is also known that vitamin D functions as a general suppressor of the immune system, including the activated B- and T- lymphocytes, and especially the T-helper cells. Some studies also show that 1,25(OH)2D3 affects several major endocrine processes, such as TRH/TSH action and pancreatic insulin secretion, with the subsequent regulation of glucose homeostasis, and likewise regulates key hepatic genes affecting lipid metabolism. Therefore, vitamin D can be considered an essential nutrient affecting many pathways of mammalian homeostasis.

This Special Issue invites original research and review papers on the role of vitamin D in health and disease.

Dr. Jose M. Valdivielso
Guest Editor

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• vitamin D
• calcitriol
• vitamin D receptor
• diabetes
• cardiovascular risk
• immunity