Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats
| Autor: | Fumi Takemoto, Keitaro Yokoyama, Akira Yamada, Kiyoshi Kurokawa, Taketoshi Inokami, Shigeko Hara, Shunya Uchida, Toshimasa Shinki |
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| Rok vydání: | 2003 |
| Předmět: |
Male
renal failure medicine.medical_specialty Vitamin D3 24-Hydroxylase Nephron vitamin D metabolites Biology Kidney Nephrectomy Calcitriol receptor Gene Expression Regulation Enzymologic Rats Sprague-Dawley Cytochrome P-450 Enzyme System secondary hyperparathyroidism Internal medicine Blood plasma medicine Vitamin D and neurology vitamin D receptor Animals RNA Messenger Northern blot Vitamin D Receptor 25-Hydroxyvitamin D3 1-alpha-Hydroxylase messenger RNA Phosphorus Blotting Northern medicine.disease Rats Disease Models Animal Low Density Lipoprotein Receptor-Related Protein-2 medicine.anatomical_structure Endocrinology Parathyroid Hormone Nephrology Steroid Hydroxylases Kidney Failure Chronic Receptors Calcitriol Calcium Secondary hyperparathyroidism |
| Zdroj: | Kidney International. 64:414-420 |
| ISSN: | 0085-2538 |
| Popis: | 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 D 3 -1α-hydroxylase), CYP24 (25-hydroxyvitamin D 3 -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 ± 0.02mg/dL in the sham-operated and 0.93 ± 0.15mg/dL in the nephrectomized rats, and both values remained constant up to week 8. Plasma concentrations of 25(OH)D 3 , 1α,25(OH) 2 D 3, and 24,25(OH) 2 D 3 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 1α,25(OH) 2 D 3 in the face of reduced nephron mass and/or megalin expression. |
| Databáze: | OpenAIRE |
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