"Phosphatonins" and the regulation of phosphorus homeostasis.
Phosphate ions are critical for normal bone mineralization, and phosphate plays a vital role in a number of other biological processes such as signal transduction, nucleotide metabolism, and enzyme regulation. The study of rare disorders associated with renal phosphate wasting has resulted in the discovery of a number of proteins [fibroblast growth factor 23 (FGF-23), secreted frizzled related protein 4 (sFRP-4), matrix extracellular phosphoglycoprotein, and FGF 7 (FGF-7)] that decrease renal sodium-dependent phosphate transport in vivo and in vitro. The "phosphatonins," FGF-23 and sFRP-4, also inhibit the synthesis of 1alpha,25-dihydroxyvitamin D, leading to decreased intestinal phosphate absorption and further reduction in phosphate retention by the organism. In this review, we discuss the biological properties of these proteins, alterations in their concentrations in various clinical disorders, and their possible physiological role.
Berndt
Theresa J
TJ
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic Rochester, Mayo College of Medicine, MN 55905, USA.
Schiavi
Susan
S
Kumar
Rajiv
R
D000328:Adult; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007408:Intestinal Absorption / Q000502:physiology; D007668:Kidney / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D009369:Neoplasms / Q000150:complications; D010018:Osteomalacia / Q000209:etiology / Q000503:physiopathology; D010750:Phosphoproteins / Q000502:physiology; D010758:Phosphorus / Q000378:metabolism*; D000094742:Secreted Frizzled-Related Proteins
D016326:Extracellular Matrix Proteins; D051523:Fibroblast Growth Factor 7; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D010758:Phosphorus; C000717427:FGF23 protein, human; C496453:FGF7 protein, human; C000717428:Fgf23 protein, mouse; C486579:MEPE protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins