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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #182513
Title: GENE PROFILING THE EFFECTS OF CALCIUM DEFICIENCY VERSUS 1,25-DIHYDROXYVITAMIN D INDUCED HYPERCALCEMIA IN RAT KIDNEY CORTEX

Author
item BAJWA, A - VIRGINIA COMMONWEALTH UNI
item Horst, Ronald
item BECKMAN, MATTHEW - VIRGINIA COMMONWEALTH UNI

Submitted to: Archives of Biochemistry and Biophysics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/23/2005
Publication Date: 6/15/2005
Citation: Bajwa, A., Horst, R.L., Beckman, M.J. 2005. Gene profiling the effects of calcium deficiency versus 1,25-dihydroxyvitamin D induced hypercalcemia in rat kidney cortex. Archives Of Biochemistry and Biophysics. 438(2):182-194.

Interpretive Summary: Vitamin D is required for the body to build strong healthy bones and teeth. In order to do its job vitamin D must be “activated”. The activated form of vitamin D is produced by the action of an enzyme located in the proximal tubule of the kidney know as the 1-hydroxylase. The compound produced, 1,25-dihydroxyvitamin D, then acts at the intestine and kidney to cause calcium to enter the body and blood calcium to be elevated. The goal of this study was to better define the intermediates involved in regulating the kidney 1-hydroxylase and ultimate production of 1,25-dihydroxyvitamin D. To do this, oligonucleotide microarray analysis was utilized between two conditionally opposing models of calcium metabolism characterized by low blood calcium on one end and high blood calcium on the other. This gene profiling approach allowed for mapping of the vitamin D endocrine system strictly based upon in vivo responses to coordinated calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D actions. The data suggest that the molecular regulation of the 1-hydroxylase is under the influence of several biological factors and allowed us to develop a better understanding of the specialized role of epithelial cells in the kidney proximal tubule as a main endocrine cell of the vitamin D activation system.

Technical Abstract: Determinants involved in the activation and repression of 1,25-dihydroxyvitamin D synthesis in renal cortex by changes in extracellular calcium were studied. Cortical kidney RNA isolated from hypocalcemic (LC) rats generated by a low calcium diet, and hypercalcemic (HC) rats generated by a normal calcium diet and 2 sequential 1 ug doses of 1,25-dihydroxyvitamin D. Among the genes up-regulated were 1-hydroxylase (4.6-fold) in the LC group and high differential gene expression of the 1,25-dihydroxyvitamin D receptor (4.0-fold) and 24-hydroxylase (10.4-fold) in the HC group. Moreover, the exposure of renal cortex to LC versus HC conditions revealed a high differential expression of a PKA-dominated pathway involving CBP interacting protein, the globulin activating factor (GATA-1) and the c-AMP response element binding protein (CREB) transcription factors in the LC model. In the HC model, elevated renal cortex gene expression of several growth factors, peptide receptors and intracellular signaling molecules depict a role for calcium sensing receptor activation and receptor tyrosine kinase signaling in 1,25-dihydroxyvitamin D-mediated gene activation and repression of 1-hydroxylase.