Modulation of renal Ca2+ transport protein genes by dietary Ca2+ and 1,25‐dihydroxyvitamin D3 in 25hydroxyvitamin D3‐1α‐hydroxylase knockout mice

JGJ Hoenderop, O Dardenne, M Van Abel… - The FASEB …, 2002 - Wiley Online Library
JGJ Hoenderop, O Dardenne, M Van Abel, AWCM Van Der Kemp, CH Van Os…
The FASEB journal, 2002Wiley Online Library
Pseudovitamin D‐deficiency rickets (PDDR) is an autosomal disease characterized by
hyperparathyroidism, rickets, and undetectable levels of 1, 25‐dihydroxyvitaminD3 (1, 25
(OH) 2D3). Mice in which the 25hydroxyvitamin D3‐1α‐hydroxylase (1α‐OHase) gene was
inactivated presented the same clinical phenotype as patients with PDDR and were used to
study renal expression of the epithelial Ca2+ channel (ECaC1), the calbindins, Na+/Ca2+
exchanger (NCX1), and Ca2+‐ATPase (PMCA1b). Serum Ca2+ (1.20±0.05 mM) and …
Abstract
Pseudovitamin D‐deficiency rickets (PDDR) is an autosomal disease characterized by hyperparathyroidism, rickets, and undetectable levels of 1,25‐dihydroxyvitaminD3 (1,25(OH)2D3). Mice in which the 25hydroxyvitamin D3‐1α‐hydroxylase (1α‐OHase) gene was inactivated presented the same clinical phenotype as patients with PDDR and were used to study renal expression of the epithelial Ca2+ channel (ECaC1), the calbindins, Na+/Ca2+ exchanger (NCX1), and Ca2+‐ATPase (PMCA1b). Serum Ca2+ (1.20±0.05 mM) and mRNA/ protein expression of ECaC1 (41±3%), calbindin‐D28K (31±2%), calbindin‐D9K (58±7%), NCX1 (10±2%), PMCA1b (96±4%) were decreased in 1α‐OHase−/−mice compared with 1α‐OHase+/‐littermates. Feeding these miceaCa2+‐enriched diet normalized serum Ca2+ levels and expression of Ca2+ proteins except for calbindin‐D9K expression. 1,25(OH)2D3 repletion resulted in increased expression of Ca2+ transport proteins and normalization of serum Ca2+ levels. Localization of Ca2+ transport proteins was clearly polarized in which ECaC1 was localized along the apical membrane, calbindin‐D28K in the cytoplasm, and calbindin‐D9K along the apical and basolateral membranes, resulting in a comprehensive mechanism facilitating renal transcellular Ca2+ transport. This study demonstrated that high dietary Ca2+ intake is an important regulator of the renal Ca2+ transport proteins in 1,25(OH)2D3‐deficient status and thus contributes to the normalization of blood Ca2+ levels.—Hoenderop, J. G. J., Dardenne, O., van Abel, M., van der Kemp, A. W. C. M., van Os, C. H., St.—Arnaud, R., Bindels, R. J. M. Modulation of renal Ca2+ transport protein genes by dietary Ca2+ and 1,25‐dihydroxyvitamin D3 in 25 hydroxyvitamin D3‐1α‐hydroxylase knockout mice. FASEB J. 16, 1398–1406 (2002)
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