期刊
NEPHROLOGY DIALYSIS TRANSPLANTATION
卷 28, 期 12, 页码 2983-2993出版社
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gft358
关键词
Ca2+-sensing receptor; electrolyte disturbances; hypomagnesaemia; mouse; parvalbumin
资金
- Dutch Organization for Scientific Research [VENI ZonMw 916.12.046]
- Dutch Kidney foundation [C08.2252]
- European Science Foundation
Magnesium (Mg-2) is an essential electrolyte with important physiological functions. Consequently, hypomagnesaemia, an electrolyte disorder frequently diagnosed in critically ill patients, can have life-threatening consequences. The kidney plays a central role in the regulation of the Mg-2 balance. The present study investigated the molecular consequences of dietary Mg-2 restriction on renal Mg-2 transporters. Two groups of 10 mice were fed a Mg-2-deficient diet or a Mg-2-enriched diet for 2weeks. Serum and urine electrolyte concentrations were assayed. Next, renal mRNA expression levels of Mg-2-related genes were measured to determine their sensitivity to the dietary Mg-2 content. Subsequently, parvalbumin (PV) and the thiazide-sensitive Na-Cl cotransporter (NCC), both co-expressed in the distal convoluted tubule (DCT) with TRPM6, were further analysed at the protein level using immunoblotting and immunohistochemistry. Serum and urine electrolyte measurements revealed that dietary Mg-2 restriction resulted in significant reduction of serum Mg-2 and Ca-2 levels, and that the urinary excretion of these ions was also markedly reduced, while phosphate (P-i) excretion was significantly increased. In addition, the serum FGF23 level was markedly increased, whereas P-i was not significantly changed in the Mg-2-restricted mouse group. The renal abundance of hepatocyte nuclear factor 1 homeobox B (HNF1B) and the epithelial Mg-2 channel TRPM6 were increased in response to dietary Mg-2 restriction, whereas other magnesiotropic transporters were not affected. PV abundance was upregulated, while NCC was significantly downregulated. Furthermore, the expression levels of the epithelial Ca-2 channel TRPV5 and calbindin-D-28K were markedly reduced in the low Mg-2 group. Our data indicate an essential adaptive role for DCT during hypomagnesaemia since TRPM6, HNF1B, PV and NCC expression levels were adjusted. Moreover, hypomagnesaemia resulted in severe changes in Ca-2 and P-i reabsorption and expression levels of calciotropic proteins.
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