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

Abstract

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

• Authors: 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
• Journal: Pflugers Archiv : European journal of physiology (Pflugers Arch) Vol. 451 Issue 4 Pg. 579-87 (Jan 2006) ISSN: 0031-6768 [Print] Germany
• PMID: 16151791 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins
• SFRP4 protein, human
• Sodium-Phosphate Cotransporter Proteins, Type IIa

Topics

• Animals
• Cells, Cultured
• Humans
• Kidney Tubules, Proximal (cytology, drug effects, metabolism)
• Male
• Opossums
• Proto-Oncogene Proteins (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Sodium-Phosphate Cotransporter Proteins, Type IIa (metabolism)