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Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats

Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats,10.1046/j.1523-1755.2003.00114.x,Kidney Internationa

Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats   (Citations: 17)
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Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats.BackgroundRegulation 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 D3-1α-hydroxylase), CYP24 (25-hydroxyvitamin D3-24-hydroxylase), and vitamin D receptor in relation to megalin, recently found to participate in renal vitamin D metabolism.MethodsA 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.ResultsPlasma 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, 1α,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.ConclusionCoordinated 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)2D3 in the face of reduced nephron mass and/or megalin expression.
Journal: Kidney International - KIDNEY INT , vol. 64, no. 2, pp. 414-420, 2003
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