Gene expression profiles in rat intestine identify pathways for 1,25-dihydroxyvitamin D3 stimulated calcium absorption and clarify its immunomodulatory properties

Microarray technology has been used to discover 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) induced gene expression changes in rat small intestine in vivo. Here, we report gene expression changes related to intestinal absorption or transport, the immune system and angiogenesis in response to 1,25-(OH)(2)D-3. Vitamin D deficient rats were intrajugularly given vehicle or vehicle containing 730 ng of 1,25-(OH)(2)D-3/kg of body weight. Intestinal mRNA was harvested from duodenal mucosa at 15 min, 1, 3, and 6 h post-injection and studied by Affymetrix microarrays. Genes significantly affected by 1,25-(OH)(2)D-3 were confirmed by quantitative RT-PCR with remarkable agreement. The most strongly affected gene in intestine was CYP24 with 97-fold increase at 6 h post-1,25-(OH)(2)D-3 treatment. Intestinal calcium absorption genes: TRPV5, TRPV6, calbindin D-9k, and Ca2+ dependent ATPase all were upregulated in response to 1,25-(OH)(2)D-3, supporting the currently accepted mechanism of 1,25-(OH)(2)D-3 induced transcellular calcium transport. However, a 1,25-(OH)(2)D-3 suppression of several intra-/intercellular matrix modeling proteins such as sodium/potassium ATPase, claudin 3, aquaporin 8, cadherin 17, and RhoA suggests a vitamin D regulation of tight junction permeability and paracellular calcium transport. Several other genes related to the immune system and angiogenesis whose expression was changed in response to 1,25-(OH)(2)D-3 provided evidence for an immunomodulatory and anti-angiogenic role of 1,25-(OH)(2)D-3. (C) 2004 Elsevier Inc. All rights reserved.