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| - Abstract Microarray technology has been used to discover 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) 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)2D3. Vitamin D deficient rats were intrajugularly given vehicle or vehicle containing 730ng of 1,25-(OH)2D3/kg of body weight. Intestinal mRNA was harvested from duodenal mucosa at 15min, 1, 3, and 6h post-injection and studied by Affymetrix microarrays. Genes significantly affected by 1,25-(OH)2D3 were confirmed by quantitative RT-PCR with remarkable agreement. The most strongly affected gene in intestine was CYP24 with 97-fold increase at 6h post-1,25-(OH)2D3 treatment. Intestinal calcium absorption genes: TRPV5, TRPV6, calbindin D9k, and Ca2+ dependent ATPase all were up-regulated in response to 1,25-(OH)2D3, supporting the currently accepted mechanism of 1,25-(OH)2D3 induced transcellular calcium transport. However, a 1,25-(OH)2D3 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)2D3 provided evidence for an immunomodulatory and anti-angiogenic role of 1,25-(OH)2D3.
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