Potentiated 1,25(OH)2D3-induced 24-hydroxylase gene expression in uremic rat intestine.
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.
Koyama
H
H
Second Department of Internal Medicine, Osaka City University Medical School, Japan.
Inaba
M
M
Nishizawa
Y
Y
Ishimura
E
E
Imanishi
Y
Y
Hini
M
M
Furuyama
T
T
Takagi
H
H
Morii
H
H
D000818:Animals; D015152:Blotting, Northern; D002117:Calcitriol / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004386:Duodenum / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D007422:Intestines / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D013250:Steroid Hydroxylases / Q000235:genetics*; D014511:Uremia / Q000201:enzymology*; D065668:Vitamin D3 24-Hydroxylase
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol