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Regulation of (pro)renin receptor expression in mIMCD via the GSK-3?-NFAT5-SIRT-1
signaling pathway
#MMPMID24990896
Quadri S
; Siragy HM
Am J Physiol Renal Physiol
2014[Sep]; 307
(5
): F593-600
PMID24990896
show ga
The localization and regulation of (pro)renin receptor (PRR) expression in kidney
collecting duct cells are not well established. We hypothesized that low salt
(LS) contributes to the regulation of PRR expression in these cells via the
GSK-3?-NFAT5-sirtuin1 (SIRT-1) signaling pathway. Mouse inner medullary
collecting duct (mIMCD) cells were treated with NaCl at 130 (normal salt; NS), 63
(LS), or 209 mM (high salt; HS) alone or in combination with NFAT5 scrambled
small interfering (si) RNA, NFAT5 siRNA, or the SIRT-1 inhibitor EX-527. Compared
with NS, LS increased the mRNA and protein expression of PRR by 71% and 69% (P <
0.05), and reduced phosphorylation of GSK-3? by 62% (P < 0.01), mRNA and protein
expressions of NFAT5 by 65% and 45% (P < 0.05), and SIRT-1 by 44% and 50% (P <
0.01), respectively. LS also enhanced p65 NF-?B by 102% (P < 0.01). Treatment
with HS significantly reduced the mRNA and protein expression of PRR by 32% and
23% (P < 0.05), and increased the mRNA and protein expression of NFAT5 by 39% and
45% (P < 0.05) and SIRT-1 by 51% and 56% (P < 0.05), respectively. HS+NFAT5 siRNA
reduced the mRNA and protein expression of NFAT5 by 51% and 35% (P < 0.01) and
increased the mRNA and protein expression of PRR by 148% and 70% (P < 0.01),
respectively. HS+EX-527 significantly increased the mRNA and protein expression
of PRR by 96% and 58% (P < 0.05), respectively. We conclude that expression of
PRR in mIMCD cells is regulated by the GSK-3?-NFAT5- SIRT-1 signaling pathway.
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