Hormones – Cytokines – Signalling
Kidney International (2003) 64, 414–420; doi:10.1046/j.1523-1755.2003.00114.x
Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats
Fumi Takemoto, Toshimasa Shinki, Keitaro Yokoyama, Taketoshi Inokami, Shigeko Hara, Akira Yamada, Kiyoshi Kurokawa and Shunya Uchida
Kidney Center, Toranomon Hospital, Tokyo, Japan; Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan; Molecular and Cellular Nephrology, Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan; and Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan
Correspondence: Fumi Takemoto, M.D., Kidney Center, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470 Japan. E-mail: ftakemoto-ind@umin.ac.jp
Received 16 May 2002; Revised 2 September 2002; Re-revised 23 February 2003; Accepted 25 March 2003.
Abstract
Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats.
Background
Regulation of vitamin D hydroxylase genes in the early stage of chronic renal failure is not fully understood. Using nephrectomized rats, we examined changes in mRNA levels of CYP27B1 (25-hydroxyvitamin D3-1
-hydroxylase), CYP24 (25-hydroxyvitamin D3-24-hydroxylase), and vitamin D receptor in relation to megalin, recently found to participate in renal vitamin D metabolism.
Methods
A rat model of moderate renal failure was induced by 3/4 nephrectomy. Plasma parameters, including vitamin D metabolite concentrations, were measured at weeks 2, 4 and 8, and poly(A)+ RNA extracted from the remnant kidneys was subjected to Northern blot hybridization.
Results
Plasma creatinine concentration at week 2 was 0.40 
0.02 mg/dL in the sham-operated and 0.93 0.15 mg/dL in the nephrectomized rats, and both values remained constant up to week 8. Plasma concentrations of 25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 were unchanged between nephrectomized and sham-operated rats at week 8. Intact parathyroid hormone (PTH) increased at week 8 in nephrectomized rats. CYP27B1 mRNA in nephrectomized rats did not vary at week 2, but increased approximately two- and four-fold at weeks 4 and 8, respectively, compared to the sham-operated rats. CYP24 and megalin mRNAs, on the other hand, began to decline as early as at week 2 in nephrectomized rats and kept decreasing throughout the experiment. The expression of vitamin D receptor was modestly but significantly decreased only at week 8.
Conclusion
Coordinated and reciprocal alterations of the increase in CYP27B1 mRNA and the decrease in CYP24 mRNA may play a pivotal role in maintaining the plasma level of 1,25(OH)2D3 in the face of reduced nephron mass and/or megalin expression.
Keywords:
renal failure, secondary hyperparathyroidism, vitamin D metabolites, vitamin D receptor, messenger RNA
