The roles of specific genes implicated as circulating factors involved in normal and disordered phosphate homeostasis: frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 23.
Normal serum phosphate (Pi) concentrations are relatively tightly controlled by endocrine mediators of Pi balance. Recent data involving several disorders of Pi homeostasis have shed new light on the regulation of serum Pi balance. It has been hypothesized that circulating phosphaturic factors, or phosphatonins, exist that, when present at high serum concentrations, directly act on the kidney to induce renal Pi wasting. This review will focus upon recently discovered factors that are overexpressed in tumors associated with tumor-induced osteomalacia and have reported activity consistent with effecting Pi balance in vivo. Currently, the best-characterized group of phosphatonin-like polypeptides includes secreted frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor-23. Our understanding of these factors will, in the short term, aid us in understanding normal Pi balance and, in the future, help to design novel therapeutic strategies for disorders of Pi handling.
White
Kenneth E
KE
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Larsson
Tobias E
TE
Econs
Michael J
MJ
D000818:Animals; D004700:Endocrine System Diseases / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics*; D051379:Mice; D009506:Nevus / Q000235:genetics; D010009:Osteochondrodysplasias / Q000235:genetics; D010279:Parathyroid Diseases / Q000235:genetics; D010710:Phosphates / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics; D000094742:Secreted Frizzled-Related Proteins
D016326:Extracellular Matrix Proteins; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D006023:Glycoproteins; D010710:Phosphates; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C486579:MEPE protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins