title: FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis.
abstract: Fibroblast growth factor 23 (FGF-23) and Klotho are secretory proteins that regulate mineral-ion metabolism. Fgf-23(-/-) or Klotho(-/-) knockout mice exhibit several pathophysiological processes consistent with premature aging including severe atrophy of tissues. We show that the signal transduction pathways initiated by FGF-23-Klotho prevent tissue atrophy by stimulating proliferation and preventing apoptosis caused by excessive systemic vitamin D. Because serum levels of active vitamin D are greatly increased upon genetic ablation of Fgf-23 or Klotho, we find that these molecules have a dual role in suppression of apoptotic actions of vitamin D through both negative regulation of 1alpha-hydroxylase expression and phosphoinositide-3 kinase-dependent inhibition of caspase activity. These data provide new insights into the physiological roles of FGF-23 and Klotho.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: Damian
authors.initials: D
authors.lastname: Medici
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Razzaque
authors.forename: Stephelynn
authors.initials: S
authors.lastname: Deluca
authors.forename: Trent L
authors.initials: TL
authors.lastname: Rector
authors.forename: Bo
authors.initials: B
authors.lastname: Hou
authors.forename: Kihwa
authors.initials: K
authors.lastname: Kang
authors.forename: Regina
authors.initials: R
authors.lastname: Goetz
authors.forename: Moosa
authors.initials: M
authors.lastname: Mohammadi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuro-O
authors.forename: Bjorn R
authors.initials: BR
authors.lastname: Olsen
authors.forename: Beate
authors.initials: B
authors.lastname: Lanske
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001284:Atrophy; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins