MEDLINE Journals

    Vitamin D: molecular mechanism of action.

    Christakos S, Dhawan P, Benn B, et al. 
    Ann N Y Acad Sci 2007 Nov.:340-8.

    Vitamin D maintains calcium homeostasis and is required for bone development and maintenance. Recent evidence has indicated an interrelationship between vitamin D and health beyond bone, including effects on cell proliferation and on the immune system. New developments in our lab related to the function and regulation of target proteins have provided novel insights into the mechanisms of vitamin D action. Studies in our lab have shown that the calcium-binding protein, calbindin, which has been reported to be a facilitator of calcium diffusion, also has an important role in protecting against apoptotic cell death in different tissues including protection against cytokine destruction of osteoblastic and pancreatic beta cells. These findings have important implications for the therapeutic intervention of many disorders including diabetes and osteoporosis. Recent studies in our laboratory of intestinal calcium absorption using calbindin-D(9k) null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inducible epithelial calcium channel, TRPV6, provide evidence for the first time of calbindin-D(9k) and TRPV6 independent regulation of active calcium absorption. Besides calbindin, the other major target of 1,25(OH)(2)D(3) in intestine and kidney is 25(OH)D(3) 24 hydroxylase (24(OH)ase), which is involved in the catabolism of 1,25(OH)(2)D(3). In our laboratory we have identified various factors that cooperate with the vitamin D receptor in regulating 24(OH)ase expression including C/EBP beta, SWI/SNF (complexes that remodel chromatin using the energy of ATP hydrolysis) and the methyltransferases, CARM1 and G9a. Evidence is also presented for C/EBP beta as a nuclear coupling factor that coordinates regulation of osteopontin by 1,25(OH)(2)D(3) and PTH. Our findings define novel mechanisms that may be of fundamental importance in understanding how 1,25(OH)(2)D(3) mediates its multiple biological effects.

    Gene Expression Regulation
    S100 Calcium Binding Protein G
    TRPV Cation Channels
    Vitamin D


    Pub Type(s)
    Journal Article Review
    PubMed ID


    Content Manager
    Related Content

    New insights into the function and regulation of vitamin D target proteins.

    Compensatory induction of the TRPV6 channel in a calbindin-D9k knockout mouse: Its regulation by 1,25-hydroxyvitamin D3.

    Effects of vitamin D compounds on renal and intestinal Ca2+ transport proteins in 25-hydroxyvitamin D3-1alpha-hydroxylase knockout mice.

    The novel vitamin D analog ZK191784 as an intestine-specific vitamin D antagonist.

    Mechanisms involved in vitamin D mediated intestinal calcium absorption and in non-classical actions of vitamin D.

    Vitamin D target proteins: function and regulation.

    Calcium channel TRPV6 expression in human duodenum: different relationships to the vitamin D system and aging in men and women.

    Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D₃-enhanced duodenal calcium transport in male mice.