Matrix Extracellular Phosphoglycoprotein Inhibits Phosphate Transport

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2008 Nov 14

PMID 19005008

Citations 28

Authors

Joanne Marks

Linda J Churchill

Edward S Debnam

Robert J Unwin

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan.

Chen H, Chiang H, Chang D, Cheng C, Wang C, Lu T Nat Commun. 2024; 15(1):9317.

PMID: 39472450 PMC: 11522641. DOI: 10.1038/s41467-024-53516-7.

The Intricacies of Renal Phosphate Reabsorption-An Overview.

Walker V Int J Mol Sci. 2024; 25(9).

PMID: 38731904 PMC: 11083860. DOI: 10.3390/ijms25094684.

Genetics of osteopontin in patients with chronic kidney disease: The German Chronic Kidney Disease study.

Cheng Y, Li Y, Scherer N, Grundner-Culemann F, Lehtimaki T, Mishra B PLoS Genet. 2022; 18(4):e1010139.

PMID: 35385482 PMC: 9015153. DOI: 10.1371/journal.pgen.1010139.

Renal Contributions to Age-Related Changes in Mineral Metabolism.

Irsik D, Bollag W, Isales C JBMR Plus. 2021; 5(10):e10517.

PMID: 34693188 PMC: 8520061. DOI: 10.1002/jbm4.10517.

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.

Palma-Lara I, Perez-Ramirez M, Garcia Alonso-Themann P, Espinosa-Garcia A, Godinez-Aguilar R, Bonilla-Delgado J Int J Mol Sci. 2021; 22(15).

PMID: 34360805 PMC: 8348777. DOI: 10.3390/ijms22158039.

References

Kolek O, Hines E, Jones M, LeSueur L, Lipko M, Kiela P . 1alpha,25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol. 2005; 289(6):G1036-42. DOI: 10.1152/ajpgi.00243.2005. View

Armbrecht H, Boltz M, Hodam T, Kumar V . Differential responsiveness of intestinal epithelial cells to 1,25-dihydroxyvitamin D3--role of protein kinase C. J Endocrinol. 2001; 169(1):145-51. DOI: 10.1677/joe.0.1690145. View

Liu S, Brown T, Zhou J, Xiao Z, Awad H, Guilak F . Role of matrix extracellular phosphoglycoprotein in the pathogenesis of X-linked hypophosphatemia. J Am Soc Nephrol. 2005; 16(6):1645-53. PMC: 1484502. DOI: 10.1681/ASN.2004121060. View

Brown A, Zhong M, Finch J, Ritter C, McCracken R, Morrissey J . Rat calcium-sensing receptor is regulated by vitamin D but not by calcium. Am J Physiol. 1996; 270(3 Pt 2):F454-60. DOI: 10.1152/ajprenal.1996.270.3.F454. View

Chattopadhyay N, Cheng I, Rogers K, Riccardi D, Hall A, Diaz R . Identification and localization of extracellular Ca(2+)-sensing receptor in rat intestine. Am J Physiol. 1998; 274(1):G122-30. DOI: 10.1152/ajpgi.1998.274.1.G122. View

Eto N, Tomita M, Hayashi M . NaPi-mediated transcellular permeation is the dominant route in intestinal inorganic phosphate absorption in rats. Drug Metab Pharmacokinet. 2006; 21(3):217-21. DOI: 10.2133/dmpk.21.217. View

Gama L, Breitwieser G . Ca2+-sensing receptors in intestinal epithelium. Am J Physiol. 1997; 273(4):C1168-75. DOI: 10.1152/ajpcell.1997.273.4.C1168. View

Jain A, Fedarko N, Collins M, Gelman R, Ankrom M, Tayback M . Serum levels of matrix extracellular phosphoglycoprotein (MEPE) in normal humans correlate with serum phosphorus, parathyroid hormone and bone mineral density. J Clin Endocrinol Metab. 2004; 89(8):4158-61. DOI: 10.1210/jc.2003-032031. View

Dobbie H, Unwin R, Faria N, Shirley D . Matrix extracellular phosphoglycoprotein causes phosphaturia in rats by inhibiting tubular phosphate reabsorption. Nephrol Dial Transplant. 2007; 23(2):730-3. DOI: 10.1093/ndt/gfm535. View

10.

Goestemeyer A, Marks J, Srai S, Debnam E, Unwin R . GLUT2 protein at the rat proximal tubule brush border membrane correlates with protein kinase C (PKC)-betal and plasma glucose concentration. Diabetologia. 2007; 50(10):2209-17. DOI: 10.1007/s00125-007-0778-x. View

11.

Rowe P, de Zoysa P, Dong R, Wang H, White K, Econs M . MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. Genomics. 2000; 67(1):54-68. DOI: 10.1006/geno.2000.6235. View

12.

Murer H, Hernando N, Forster L, Biber J . Molecular mechanisms in proximal tubular and small intestinal phosphate reabsorption (plenary lecture). Mol Membr Biol. 2001; 18(1):3-11. DOI: 10.1080/09687680010019357. View

13.

Bresler D, Bruder J, Mohnike K, Fraser W, Rowe P . Serum MEPE-ASARM-peptides are elevated in X-linked rickets (HYP): implications for phosphaturia and rickets. J Endocrinol. 2004; 183(3):R1-9. PMC: 3357083. DOI: 10.1677/joe.1.05989. View

14.

Sommer S, Berndt T, Craig T, Kumar R . The phosphatonins and the regulation of phosphate transport and vitamin D metabolism. J Steroid Biochem Mol Biol. 2007; 103(3-5):497-503. DOI: 10.1016/j.jsbmb.2006.11.010. View

15.

Fisher L, Fedarko N . Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins. Connect Tissue Res. 2003; 44 Suppl 1:33-40. View

16.

Brown E, Pollak M, Hebert S . Sensing of extracellular Ca2+ by parathyroid and kidney cells: cloning and characterization of an extracellular Ca(2+)-sensing receptor. Am J Kidney Dis. 1995; 25(3):506-13. DOI: 10.1016/0272-6386(95)90118-3. View

17.

Marks J, Churchill L, Srai S, Biber J, Murer H, Jaeger P . Intestinal phosphate absorption in a model of chronic renal failure. Kidney Int. 2007; 72(2):166-73. DOI: 10.1038/sj.ki.5002292. View

18.

Hebert S, Cheng S, Geibel J . Functions and roles of the extracellular Ca2+-sensing receptor in the gastrointestinal tract. Cell Calcium. 2004; 35(3):239-47. DOI: 10.1016/j.ceca.2003.10.015. View

19.

Radanovic T, Wagner C, Murer H, Biber J . Regulation of intestinal phosphate transport. I. Segmental expression and adaptation to low-P(i) diet of the type IIb Na(+)-P(i) cotransporter in mouse small intestine. Am J Physiol Gastrointest Liver Physiol. 2005; 288(3):G496-500. DOI: 10.1152/ajpgi.00167.2004. View

20.

Brown A, Dusso A, Slatopolsky E . Vitamin D. Am J Physiol. 1999; 277(2):F157-75. DOI: 10.1152/ajprenal.1999.277.2.F157. View