Potentiated 1,25(OH)2D3-induced 24-hydroxylase gene expression in uremic rat intestine

Abstract

24-Hydroxylase has been considered a major enzyme regulating metabolism of circulating 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]. To understand the metabolism of 1,25(OH)2D3 in chronic renal failure, we examined 1,25(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) gene expression in the intestine of uremic rats. Northern blot and dot blot analyses showed that the induction of duodenal 24-hydroxylase gene expression was 2.0- to 3.8-fold greater in uremic rats than in sham-operated rats (P < 0.05, Student's t-test) at 6 h after 1,25(OH)2D3 administration. Gene induction of calbindin D9k by 1,25(OH)2D3 was not augmented in uremic group. In situ hybridization analysis revealed that the induction of 24-hydroxylase mRNA by 1,25(OH)2D3 was observed exclusively in the columnar epithelium of the crypt and the lower part of the villi, suggesting that the stage of epithelial cell differentiation is a major determinant of 1,25(OH)2D3-induced 24-hydroxylase gene expression. In uremia, 1,25(OH)2D3-induced 24-hydroxylase gene expression was accelerated selectively, possibly because of poorly differentiated epithelial cells.