Mechanisms involved in vitamin D mediated intestinal calcium absorption and in non-classical actions of vitamin D.
Recent studies in our laboratory using calbindin-D9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inducible epithelial calcium channel TRPV6 provide evidence for calbindin-D9k and TRPV6 independent regulation of active intestinal calcium absorption. These findings suggest that in the knock out (KO) mice there is compensation by another calcium channel or protein and that other novel factors are involved in 1,25(OH)2D3 mediated active intestinal calcium absorption. In addition, 1,25(OH)2D3 mediated paracellular transport of calcium may have contributed to the normalization of serum calcium in the null mutant mice. 1,25(OH)2D3 downregulates cadherin-17 and upregulates claudin-2 and claudin-12 in the intestine, suggesting that 1,25(OH)2D3, by regulating these epithelial cell junction proteins, can route calcium through the paracellular path. With regard to non-classical actions, 1,25(OH)2D3 has been reported to inhibit the proliferation of a number of malignant cells and to regulate adaptive as well as innate immunity. This article will review new developments related to the function and regulation of vitamin D target proteins in classical and non-classical vitamin D target tissues that have provided novel insight into mechanisms of vitamin D action.
Christakos
Sylvia
S
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103, United States. christak@umdnj.edu
Dhawan
Puneet
P
Ajibade
Dare
D
Benn
Bryan S
BS
Feng
Jingjing
J
Joshi
Sneha S
SS
D000042:Absorption; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D002136:Calcium, Dietary / Q000378:metabolism*; D057167:Claudins; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020381:Interleukin-17 / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D064026:Calbindins; D002136:Calcium, Dietary; D057167:Claudins; C113371:Cldn2 protein, mouse; D020381:Interleukin-17; D008565:Membrane Proteins; D064030:S100 Calcium Binding Protein G; C576507:S100g protein, mouse; C488754:claudin 12 protein, mouse; D014807:Vitamin D; D002118:Calcium; D054804:Cathelicidins