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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Endocrinology
2010 ; 151
(12
): 5700-9
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trpm7 regulation of in vivo cation homeostasis and kidney function involves
stanniocalcin 1 and fgf23
#MMPMID20881241
Elizondo MR
; Budi EH
; Parichy DM
Endocrinology
2010[Dec]; 151
(12
): 5700-9
PMID20881241
show ga
The transient receptor potential melastatin 7 (trpm7) channel kinase is a primary
regulator of magnesium homeostasis in vitro. Here we show that trpm7 is an
important regulator of cation homeostasis as well as kidney function in vivo.
Using zebrafish trpm7 mutants, we show that early larvae exhibit reduced levels
of both total magnesium and total calcium. Accompanying these deficits, we show
that trpm7 mutants express higher levels of stanniocalcin 1 (stc1), a potent
regulator of calcium homeostasis. Using transgenic overexpression and morpholino
oligonucleotide knockdown, we demonstrate that stc1 modulates both calcium and
magnesium levels in trpm7 mutants and in the wild type and that levels of these
cations are restored to normal in trpm7 mutants when stc1 activity is blocked.
Consistent with defects in both calcium and phosphate homeostasis, we further
show that trpm7 mutants develop kidney stones by early larval stages and exhibit
increased levels of the anti-hyperphosphatemic factor, fibroblast growth factor
23 (fgf23). Finally, we demonstrate that elevated fgf23 expression contributes to
kidney stone formation by morpholino knockdown of fgf23 in trpm7 mutants.
Together, these analyses reveal roles for trpm7 in regulating cation homeostasis
and kidney function in vivo and implicate both stc1 and fgf23 in these processes.