The molecular mechanism of vitamin D and its association with FGF23 and Klotho.

The classic role of vitamin D (VD) is to regulate metabolism of calcium, phosphorus and the bone. It is also important in the immune system, cell proliferation and differentiation. The liganding of 1,25(OH)D-VDR triggers tight association between VDR and a retinoid X receptor (RXR). VDR-RXR heterodimer is conformed to recognize vitamin D responsive elements (VDREs) in the DNA sequence of vitamin D-regulated genes. Although the hormone receptor complex acts rapidly via nongenomic mechanisms, 1,25 (OH) D-VDR functions mainly through genomic mechanisms. 1,25 (OH) D-VDR regulates gene transcription. The vitamin D ligand, the DNA sequence of the VDRE, and the recruited coactivator/corepressor are all capable of influencing gene expression. VDREs regulated by 1,25 (OH) D-VDR have important function. By using RANKL gene chromatin loop model, it is suggested that DNA-looping and chromatin architecture play a main role in VD regulation of gene expression. Gene expression regulated by 1,25 (OH) D-VDR may delay chronic disorders of aging such as cancer, type 2 diabetes, and cardiovascular diseases. A new knowledge about the association between VD and phosphate metabolism and aging is that 1,25 (OH) D-VDR plays an important role in this metabolic pathway through FGF23 in the bone and Klotho in the kidney. Phosphate stability regulated by VD may be the mechanism of age delaying. [ABSTRACT FROM AUTHOR]