title: Novel functions of circulating Klotho.
abstract: A significant portion of the key biological functions of αKlotho (αKL) and its cognate ligand Fibroblast growth factor-23 (FGF23) have been revealed through the study of rare diseases of mineral metabolism. These findings have far reaching implications for common disorders such as chronic kidney disease-mineral bone disorder (CKD-MBD). αKL's predominant effect on mineral homeostasis is through its actions in the kidney as a co-receptor for FGF23, however emerging data has shed light on its capacity to act as a circulating factor through the cleavage of the transmembrane form of αKL ('mKL') to produce 'cleaved KL' or 'cKL'. This review summarizes new findings from studies using extended delivery of cKL to mouse models with phenotypes reflecting those arising in CKD-MBD.
authors.affiliation: Department of Medical and Molecular Genetics, Division of Molecular Genetics and Gene Therapy, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Division of Biomedical Science, Marian University School of Osteopathic Medicine, Indianapolis, IN 46222, USA.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Hum
authors.affiliation: Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: O'Bryan
authors.affiliation: Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Rosamund C
authors.initials: RC
authors.lastname: Smith
authors.affiliation: Department of Medical and Molecular Genetics, Division of Molecular Genetics and Gene Therapy, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: kenewhit@iupui.edu.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: White
mesh_terms: D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D051379:Mice; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: FGF23; Hyperphosphatemia; Hypophosphatemia; Phosphate; Vascular calcification; cKL