Naslov
Secreted frizzled-related protein-4 reduces sodium-phosphate co- transporter abundance and activity in proximal tubule cells

Autori
Berndt, T.J. ; Bielesz, B. ; Craig, T.A. ; Tebben, P.J. ; Bačić, D. ; Wagner, C.A. ; O'Brien, S. ; Schiavi, S. ; Biber, J. ; Murer, H. ; Kumar, R.

Izvornik
Pflügers Archiv European Journal of Physiology (0031-6768) 451 (2006), 4; 579-587

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
phosphatonin; sFRP-4; sodium-phosphate co-transporter; proximal tubule cells

Sažetak
The phosphatonin, secreted frizzled-related protein-4 (sFRP-4), induces phosphaturia and inhibits 25-hydroxyvitamin D 1- hydroxylase activity normally induced in response to hypophosphatemia. To determine the mechanism by which sFRP-4 alters renal phosphate (Pi) transport, we examined the effect of sFRP-4 on renal brush border membrane (BBMV) Na+- dependent Pi uptake, and the abundance and localization of the major Na+?Pi-IIa co-transporter in proximal tubules and opossum kidney (OK) cells. Infusion of sFRP-4 increased renal fractional excretion of Pi and decreased renal -catenin concentrations. The increase in renal Pi excretion with sFRP-4 infusion was associated with a 21.9?3.4% decrease in BBMV Na +-dependent Pi uptake (P<0.001) compared with a 39.5?2.1% inhibition of Na+-dependent Pi transport in renal BBMV induced by PTH (P<0.001). sFRP-4 infusion was associated with a 30.7 ?4.8% decrease in Na+?Pi-IIa co-transporter protein abundance (P<0.01) assessed by immunoblotting methods compared to a 45.4?8.8% decrease induced by PTH (P<0.001). In OK cells, sFRP-4 reduced surface expression of a heterologous Na+?Pi-IIa co-transporter. We conclude that sFRP-4 increases renal Pi excretion by reducing Na+?Pi-IIa transporter abundance in the brush border of the proximal tubule through enhanced internalization of the protein.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA