Matrix extracellular phosphoglycoprotein inhibits phosphate transport.
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 D(3), 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.
Marks
Joanne
J
Department of Physiology, University College London Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF. j.marks@medsch.ucl.ac.uk
Churchill
Linda J
LJ
Debnam
Edward S
ES
Unwin
Robert J
RJ
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000502:physiology*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism* / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C486579:MEPE protein, human; C417185:Mepe protein, rat; D010281:Parathyroid Hormone; D010710:Phosphates; D010750:Phosphoproteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23