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

Theresa J. Berndt, Bernhard Bielesz, Theodore A. Craig, Peter J. Tebben, Desa Bacic, Carsten A. Wagner, Stephen O'Brien, Susan Schiavi, Jurg Biber, Heini Murer, Rajiv Kumar

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34 Scopus citations


The phosphatonin, secreted frizzled-related protein-4 (sFRP-4), induces phosphaturia and inhibits 25-hydroxyvitamin D 1α-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 β-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.

Original languageEnglish (US)
Pages (from-to)579-587
Number of pages9
JournalPflugers Archiv European Journal of Physiology
Issue number4
StatePublished - Jan 1 2006


ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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