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

Abstract

Recent studies in our laboratory using calbindin-D 9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) inducible epithelial calcium channel TRPV6 provide evidence for calbindin-D 9k 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) 2D 3 mediated active intestinal calcium absorption. In addition, 1,25(OH) 2D 3 mediated paracellular transport of calcium may have contributed to the normalization of serum calcium in the null mutant mice. 1,25(OH) 2D 3 downregulates cadherin-17 and upregulates claudin-2 and claudin-12 in the intestine, suggesting that 1,25(OH) 2D 3, by regulating these epithelial cell junction proteins, can route calcium through the paracellular path. With regard to non-classical actions, 1,25(OH) 2D 3 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.