Protective links between vitamin D, inflammatory bowel disease and colon cancer

Figure 1 Vitamin D metabolism. Vitamin D can be obtained either through exposure to sunlight where ultraviolet B (UVB) interaction in the skin converts 7-dehydrocholesterol to vitamin D or through absorption from the diet. Vitamin D must undergo several hydroxylation steps to become an active metabolite, 1,25-dihydroxyvitamin D. The first hydroxylation step occurring mainly in liver by 25-hydroxylase produces 25-hydroxyvitamin D, the main circulating form of vitamin D. The second hydroxylation step catalyzed by 1α-hydroxylase occurs in many target tissues including kidney, intestinal epithelial cells and immune cells and generates the active form of vitamin D, 1,25-dihydroxyvitamin D. This latter form of vitamin D is a ligand for a transcription factor, vitamin D receptor (VDR), which is present in most cell types. VDR bound with 1,25-dihydroxyvitamin D translocates to the nucleus where it dimerizes with retinoid X receptor (RXR). The dimers have the ability to activate transcription of various genes containing a specific promoter region known as vitamin D response elements (VDRE) by binding to the region and recruiting transcriptional machinery.