Analysis of 1,25-Dihydroxyvitamin D ₃ Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids

Although vitamin D is critical for the function of the intestine, most studies have focused on the duodenum. We show that transgenic expression of the vitamin D receptor (VDR) only in the distal intestine of VDR null mice (KO/TG mice) results in the normalization of serum calcium and rescue of rickets. Although it had been suggested that calcium transport in the distal intestine involves a paracellular process, we found that the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-activated genes in the proximal intestine associated with active calcium transport ( Trpv6 , S100g , and Atp2b1 ) are also induced by 1,25(OH) 2 D 3 in the distal intestine of KO/TG mice.