AJP - Renal Physiology, Vol 267, Issue 6 926-F930, Copyright © 1994 by American Physiological Society
Potentiated 1,25(OH)2D3-induced 24-hydroxylase gene expression in uremic rat intestine
H. Koyama, M. Inaba, Y. Nishizawa, E. Ishimura, Y. Imanishi, M. Hini, T. Furuyama, H. Takagi and H. Morii
Second Department of Internal Medicine, Osaka City University Medical School, Japan.
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.
