REGULATION OF (PRO)RENIN RECEPTOR EXPRESSION IN mIMCD VIA GSK3β-NFAT5- SIRT-1 SIGNALING PATHWAY.

REGULATION OF (PRO)RENIN RECEPTOR EXPRESSION IN mIMCD VIA GSK3β-NFAT5- SIRT-1 SIGNALING PATHWAY. Am J Physiol Renal Physiol. 2014 Jul 2; Authors: Quadri S, Siragy HM Abstract The localization and regulation of (Pro)renin receptor expression (PRR) in the kidney collecting duct cells is not well established. We hypothesized that low salt contributes to the regulation of PRR expression in these cells via GSK3β-NFAT5-SIRT-1 signaling pathway. mIMCD were treated with NaCl at 130mM (NS), 63mM (LS) or 209mM (HS) alone or in combination with NFAT5 scrambled siRNA, NFAT5 siRNA, or the SIRT-1 inhibitor, EX527. Compared to NS, LS increased the mRNA and protein expression of PRR by 71% and 69% (P< 0.05), and reduced phosphorylation of GSK3β by 62% (P< 0.01), mRNA and protein expressions of NFAT5by 65% and 45% (P< 0.05), SIRT-1 by 44% and 50% (P< 0.01) respectively. LS also enhanced the p65 NFκB 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 expressions of NAFT5 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+EX527 significantly increased the mRNA and protein expression of PRR by 96% and 58...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research