Variable in vivo regulation of rat vitamin D-dependent genes (osteopontin, Ca,Mg-adenosine triphosphatase, and 25-hydroxyvitamin D3 24-hydroxylase): implications for differing mechanisms of regulation and involvement of multiple factors.
In these studies, the regulation of renal osteopontin (OPN), intestinal calcium pump, and renal and intestinal 25-hydroxyvitamin D3 24-hydroxylase (24OHase) was compared to the regulation of calbindin by Northern blot analysis. The time course of induction of the calbindins and calcium pump messenger RNAs (mRNAs) in vitamin D-deficient rats in response to 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] was similar [first induction 3 h after 1,25-(OH)2D3 (200 ng/100 g BW), reaching a maximum at 12-24 h]. However, the maximal induction of calbindin mRNA was greater (8.2 +/- 1.2-fold) than that of intestinal calcium pump mRNA (21.3 +/- 0.5-fold). 24-Hydroxylase mRNA showed a different time course of induction by 1,25-(OH)2D3. 24-Hydroxylase mRNA was undetectable in vitamin D-deficient rat intestine and kidney. In intestine, 24OHase mRNA was maximally induced early [3-6 h after 1,25-(OH)2D3] and did not accumulate long after 1,25-(OH)2D3 administration. Unlike the other vitamin D-regulated genes, OPN was uninduced by 1,25-(OH)2D3 in the kidney of D-deficient rats. However, in vitamin D-replete rats given 1,25-(OH)2D3 for 5 days, a significant induction in renal OPN was observed (6.0-fold; P < 0.01). Developmental studies indicated that renal 24OHase and intestinal calcium pump mRNAs, similar to calbindin-D9K mRNA, were induced at 3 weeks of age, the time of weaning when active intestinal calcium absorption is induced. A comparison of the effect of calcium status showed that low dietary calcium resulted in an induction of intestinal calcium pump as well as calbindin-D9K mRNA, consistent with the requirement for an increase in intestinal calcium absorption during dietary calcium restriction. We next examined gender- and age-related changes in the expression of these genes. Our results indicate that renal OPN mRNA increases markedly in males with aging (10-fold between 3-20 months; P < 0.01), whereas OPN mRNA levels are unchanged in females. In both males and females, significant increases (2.7- to 4.5-fold) in renal 24OHase mRNA were observed at 20 months compared to 3 months of age.(ABSTRACT TRUNCATED AT 400 WORDS)
Matkovits
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Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry-New Jersey Medical School, Newark 07103, USA.
Christakos
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D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D015152:Blotting, Northern; D017301:Ca(2+) Mg(2+)-ATPase / Q000235:genetics*; D064026:Calbindins; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002531:Cerebellum / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D007422:Intestines / Q000737:chemistry; D007668:Kidney / Q000737:chemistry; D008297:Male; D053495:Osteopontin; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000032:analysis / Q000235:genetics; D012727:Sex Characteristics; D012795:Sialoglycoproteins / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*; D013997:Time Factors; D014807:Vitamin D / Q000502:physiology*; D065668:Vitamin D3 24-Hydroxylase
D064026:Calbindins; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; C576508:S100g protein, rat; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D017301:Ca(2+) Mg(2+)-ATPase; D002117:Calcitriol; D002118:Calcium