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1,25-Dihydroxyvitamin D3 up-regulates the renal vitamin D receptor through indirect gene activation and receptor stabilization.
Arch Biochem Biophys 2005; 433(2):466-73AB

Abstract

Expression of the vitamin D receptor (VDR) in the kidney and intestine plays a major role in calcium homeostasis and the metabolism of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Calcium and 1,25(OH)(2)D(3)-mediated regulation of renal and duodenal VDR expression has been analyzed in vivo and the mechanisms responsible for the renal regulation have been studied in mouse kidney TCMK-1 cells. Vitamin D-deficient mice were maintained on diets containing either 0.02 or 0.47% calcium, with or without 50ng of 1,25(OH)(2)D(3) per day. Renal VDR levels were significantly higher in the vitamin D-deficient mice fed the 0.47% calcium diet vs. the calcium-restricted diet, and were increased 5-fold by 1,25(OH)(2)D(3) when dietary calcium was present. The renal VDR transcript was expressed at a basal level in the absence of calcium or 1,25(OH)(2)D(3); 50ng of 1,25(OH)(2)D(3) elevated renal VDR mRNA levels approximately 10-fold in the presence of calcium. Neither calcium nor 1,25(OH)(2)D(3) had any significant effect on duodenal VDR or VDR mRNA expression. In TCMK-1 cells, 1,25(OH)(2)D(3) increased receptor and VDR mRNA content in both low and adequate calcium medium. The 1,25(OH)(2)D(3)-mediated increase in VDR mRNA did not result from increased stability of the transcript. Further, the increase in mRNA was blocked by cycloheximide, indicating a requirement for protein synthesis and an indirect regulation of VDR transcription. Thus, both dietary serum calcium and 1,25-(OH)(2)D(3) are required for VDR expression in kidney but not in intestine where neither is required. The 1,25-(OH)(2)D(3) requirement can also be shown in TCMK-1 cells in vitro, while the calcium requirement was not found.

Authors+Show Affiliations

Department of Biochemistry, College of Agricultural and Life sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15581603

Citation

Healy, Kevin D., et al. "1,25-Dihydroxyvitamin D3 Up-regulates the Renal Vitamin D Receptor Through Indirect Gene Activation and Receptor Stabilization." Archives of Biochemistry and Biophysics, vol. 433, no. 2, 2005, pp. 466-73.
Healy KD, Frahm MA, DeLuca HF. 1,25-Dihydroxyvitamin D3 up-regulates the renal vitamin D receptor through indirect gene activation and receptor stabilization. Arch Biochem Biophys. 2005;433(2):466-73.
Healy, K. D., Frahm, M. A., & DeLuca, H. F. (2005). 1,25-Dihydroxyvitamin D3 up-regulates the renal vitamin D receptor through indirect gene activation and receptor stabilization. Archives of Biochemistry and Biophysics, 433(2), pp. 466-73.
Healy KD, Frahm MA, DeLuca HF. 1,25-Dihydroxyvitamin D3 Up-regulates the Renal Vitamin D Receptor Through Indirect Gene Activation and Receptor Stabilization. Arch Biochem Biophys. 2005 Jan 15;433(2):466-73. PubMed PMID: 15581603.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 1,25-Dihydroxyvitamin D3 up-regulates the renal vitamin D receptor through indirect gene activation and receptor stabilization. AU - Healy,Kevin D, AU - Frahm,Marc A, AU - DeLuca,Hector F, PY - 2004/08/30/received PY - 2004/10/01/revised PY - 2004/12/8/pubmed PY - 2005/1/28/medline PY - 2004/12/8/entrez SP - 466 EP - 73 JF - Archives of biochemistry and biophysics JO - Arch. Biochem. Biophys. VL - 433 IS - 2 N2 - Expression of the vitamin D receptor (VDR) in the kidney and intestine plays a major role in calcium homeostasis and the metabolism of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Calcium and 1,25(OH)(2)D(3)-mediated regulation of renal and duodenal VDR expression has been analyzed in vivo and the mechanisms responsible for the renal regulation have been studied in mouse kidney TCMK-1 cells. Vitamin D-deficient mice were maintained on diets containing either 0.02 or 0.47% calcium, with or without 50ng of 1,25(OH)(2)D(3) per day. Renal VDR levels were significantly higher in the vitamin D-deficient mice fed the 0.47% calcium diet vs. the calcium-restricted diet, and were increased 5-fold by 1,25(OH)(2)D(3) when dietary calcium was present. The renal VDR transcript was expressed at a basal level in the absence of calcium or 1,25(OH)(2)D(3); 50ng of 1,25(OH)(2)D(3) elevated renal VDR mRNA levels approximately 10-fold in the presence of calcium. Neither calcium nor 1,25(OH)(2)D(3) had any significant effect on duodenal VDR or VDR mRNA expression. In TCMK-1 cells, 1,25(OH)(2)D(3) increased receptor and VDR mRNA content in both low and adequate calcium medium. The 1,25(OH)(2)D(3)-mediated increase in VDR mRNA did not result from increased stability of the transcript. Further, the increase in mRNA was blocked by cycloheximide, indicating a requirement for protein synthesis and an indirect regulation of VDR transcription. Thus, both dietary serum calcium and 1,25-(OH)(2)D(3) are required for VDR expression in kidney but not in intestine where neither is required. The 1,25-(OH)(2)D(3) requirement can also be shown in TCMK-1 cells in vitro, while the calcium requirement was not found. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/15581603/125_Dihydroxyvitamin_D3_up_regulates_the_renal_vitamin_D_receptor_through_indirect_gene_activation_and_receptor_stabilization_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(04)00564-8 DB - PRIME DP - Unbound Medicine ER -