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Published ahead of print on November 12, 2008
J Am Soc Nephrol 19: 2313-2320, 2008
© 2008 American Society of Nephrology
doi: 10.1681/ASN.2008030315
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BASIC RESEARCH

Matrix Extracellular Phosphoglycoprotein Inhibits Phosphate Transport

Joanne Marks*, Linda J. Churchill*, Edward S. Debnam* and Robert J. Unwin*,{dagger}

London Epithelial Group, * Department of Physiology and {dagger} Centre for Nephrology, University College London (Royal Free Campus), London, United Kingdom

Correspondence: Dr. Joanne Marks, Department of Physiology, University College London Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF. Phone: 44-0-20-7472-6470; Fax: 44-0-20-7472-6476; E-mail: j.marks{at}medsch.ucl.ac.uk

Received for publication March 21, 2008. Accepted for publication August 18, 2008.

The role of putative humoral factors, known as phosphatonins, in phosphate homeostasis and the relationship between phosphate handling by the kidney and gastrointestinal tract are incompletely understood. Matrix extracellular phosphoglycoprotein (MEPE), one of several candidate phosphatonins, promotes phosphaturia, but whether it also affects intestinal phosphate absorption is unknown. Here, using the in situ intestinal loop technique, we demonstrated that short-term infusion of MEPE inhibits phosphate absorption in the jejunum but not the duodenum. Simultaneous measurement of urinary phosphate excretion suggests that the phosphaturic action of MEPE correlates with a significant reduction in the protein levels of the renal sodium-phosphate co-transporter NaPi-IIa in the proximal convoluted tubules of the outer renal cortex, assessed by Western blotting and immunohistochemistry. This short-term inhibitory effect of MEPE on renal and intestinal phosphate handling occurred without any changes in circulating levels of parathyroid hormone, 1,25-dihydroxyvitamin D3, or fibroblast growth factor 23. Taken together, these findings suggest that MEPE is a candidate phosphatonin involved in phosphate homeostasis, acting in both the kidney and the gastrointestinal tract.






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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673