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This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 297/3/E728    most recent 00168.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ishizawa, M. Articles by Makishima, M. PubMed PubMed Citation Articles by Ishizawa, M. Articles by Makishima, M.

Hypergravity modulates vitamin D receptor target gene mRNA expression in mice

¹Division of Biochemistry, Department of Biomedical Sciences, and ²Division of Hygiene, Department of Social Medicine, Nihon University School of Medicine, Tokyo; and ³Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan

Submitted 16 March 2009 ; accepted in final form 22 June 2009

The possibility of pathological calcium metabolism is a critical health concern introduced by long-term space travel. Because vitamin D plays an important role in calcium homeostasis, we evaluated the effects of hypergravity on the expression of genes involved in vitamin D and calcium metabolism in ICR mice. When exposed to 2G hypergravity for 2 days, the mRNA expression of renal 25-hydroxyvitamin D 24-hydroxylase (Cyp24a1) was increased and that of 25-hydroxyvitamin D 1-hydroxylase (Cyp27b1) was decreased. Although hypergravity decreased food intake and increased the expression of starvation-induced genes, the changes in Cyp24a1 and Cyp27b1 expression were not due to starvation, suggesting that hypergravity affects these genes directly. Hypergravity decreased plasma 1,25-dihydroxyvitamin D₃ levels in ICR mice, suggesting a consequence of decreased Cyp27b1 and increased Cyp24a1 expression. Although 1-hydroxyvitamin D₃ [1(OH)D₃] treatment induced the expression of vitamin D receptor (VDR) target genes in the kidney of 2G-exposed ICR mice to similar levels as controls, 1(OH)D₃ increased the intestinal expression of Cyp24a1 in ICR mice. Hypergravity-dependent changes of Cyp24a1 and Cyp27b1 expression were diminished in mice exposed to hypergravity for 14 days, which may represent an adaptation to hypergravity stress. Hypergravity exposure also increased Cyp24a1 expression in the kidney of C57BL/6J mice. We examined the effects of hypergravity on VDR-null mice and found that renal Cyp27b1 expression in VDR-null mice was decreased by hypergravity while renal Cyp24a1 expression was not detected in VDR-null mice. Thus hypergravity modifies the expression of genes involved in vitamin D metabolism.

vitamin D; vitamin D receptor; hypergravity; kidney; transcription