Abstract
Phosphate (Pi) is one of the basic necessities required for sustenance of life and its metabolism largely relies on excretory function of the kidney, a process chiefly under the endocrine control of bone-derived fibroblast growth factor 23 (FGF23). However, knowledge gap exists in understanding the regulatory loop responsible for eliciting phophaturic response to Pi treatment. Here, we reported a novel role of (pro)renin receptor (PRR) in mediating phosphaturic response to Pi treatment via upregulation of FGF23 production. Male Sprague-Dawley rats were pretreated for 5 days via osmotic pump-driven infusion of a PRR antagonist PRO20 or vehicle, and then treated with high Pi (HP) solution as drinking fluid for the last 24 h. PRO20 reduced HP-induced Pi excretion by 42%, accompanied by blunted upregulation of circulating FGF23 and parathyroid hormone (PTH) and downregulation of renal Na/Pi-IIa expression. In cultured osteoblast cells, exposure to HP induced a 1.56-fold increase in FGF23 expression, which was blunted by PRO20 or siRNA against PRR. Together, these results suggest that activation of PRR promotes phosphaturic response through stimulation of FGF23 production and subsequent downregulation of renal Na/Pi-IIa expression.
Highlights
Phosphate (Pi) is an essential nutrient and component of the human body
The results showed that the levels angiotensinogen (AGT), renin, soluble PRR (sPRR) in urine and plasma from the high Pi (HP) group were significantly increased as compared with normal Pi (NP) controls (Figure 1)
Following HP intake, the levels of circulating sPRR along with renal expression of PRR and other components of the reninangiotensin system (RAS) were all elevated in parallel with increased plasma fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH)
Summary
Phosphate (Pi) is an essential nutrient and component of the human body. Adequate phosphate balance is essential for the maintenance of fundamental cellular functions of the mammalian system, ranging from energy metabolism to mineral ion metabolism (Gaasbeek and Meinders, 2005). The kidney plays a pivotal role in maintenance of Pi homeostasis by adjustment of reabsorption and excretion (Shimada et al, 2004a; Urakawa et al, 2006). Most of the filtered Pi is reabsorbed across the proximal tubule cells (Katai et al, 1999 Giral et al, 2009). Evidence from physiological studies suggests that Na+-dependent Pi transporters in the brushborder membrane (BBM) of proximal tubular cells mediate the rate-limiting step in the overall Pi-reabsorptive process (Murer et al, 2000, 2003).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
