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

Abstract

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 alpha-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 alpha,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 alpha,25(OH)2D3 in the face of reduced nephron mass and/or megalin expression.

• Authors: Fumi Takemoto, Toshimasa Shinki, Keitaro Yokoyama, Taketoshi Inokami, Shigeko Hara, Akira Yamada, Kiyoshi Kurokawa, Shunya Uchida
• Journal: Kidney international (Kidney Int) Vol. 64 Issue 2 Pg. 414-20 (Aug 2003) ISSN: 0085-2538 [Print] United States
• PMID: 12846736 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-methyl-1,25-dihydroxyvitamin D3
• Low Density Lipoprotein Receptor-Related Protein-2
• Parathyroid Hormone
• RNA, Messenger
• Receptors, Calcitriol
• Vitamin D
• Phosphorus
• Cytochrome P-450 Enzyme System
• Steroid Hydroxylases
• Vitamin D3 24-Hydroxylase
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
• Calcium

Topics

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (genetics)
• Animals
• Blotting, Northern
• Calcium (blood)
• Cytochrome P-450 Enzyme System (genetics)
• Disease Models, Animal
• Gene Expression Regulation, Enzymologic
• Kidney (enzymology)
• Kidney Failure, Chronic (physiopathology)
• Low Density Lipoprotein Receptor-Related Protein-2 (genetics)
• Male
• Nephrectomy
• Parathyroid Hormone (blood)
• Phosphorus (blood)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Receptors, Calcitriol (genetics)
• Steroid Hydroxylases (genetics)
• Vitamin D (analogs & derivatives, blood)
• Vitamin D3 24-Hydroxylase