FGF-23 - Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis

Damian Medici, Mohammed S. Razzaque, Stephelynn DeLuca, Trent L. Rector, Bo Hou, Kihwa Kang, Regina Goetz, Moosa Mohammadi, Makoto Kuro-o, Bjorn R. Olsen, Beate Lanske

Research output: Contribution to journalArticle

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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 1α-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.

Original languageEnglish (US)
Pages (from-to)459-465
Number of pages7
JournalJournal of Cell Biology
Volume182
Issue number3
DOIs
StatePublished - Aug 11 2008

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Vitamin D
Apoptosis
Atrophy
Premature Aging
1-Phosphatidylinositol 4-Kinase
Caspases
Mixed Function Oxygenases
Knockout Mice
Minerals
Signal Transduction
Ions
Serum
fibroblast growth factor 23
klotho protein

ASJC Scopus subject areas

  • Cell Biology

Cite this

Medici, D., Razzaque, M. S., DeLuca, S., Rector, T. L., Hou, B., Kang, K., ... Lanske, B. (2008). FGF-23 - Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis. Journal of Cell Biology, 182(3), 459-465. https://doi.org/10.1083/jcb.200803024

FGF-23 - Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis. / Medici, Damian; Razzaque, Mohammed S.; DeLuca, Stephelynn; Rector, Trent L.; Hou, Bo; Kang, Kihwa; Goetz, Regina; Mohammadi, Moosa; Kuro-o, Makoto; Olsen, Bjorn R.; Lanske, Beate.

In: Journal of Cell Biology, Vol. 182, No. 3, 11.08.2008, p. 459-465.

Research output: Contribution to journalArticle

Medici, D, Razzaque, MS, DeLuca, S, Rector, TL, Hou, B, Kang, K, Goetz, R, Mohammadi, M, Kuro-o, M, Olsen, BR & Lanske, B 2008, 'FGF-23 - Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis', Journal of Cell Biology, vol. 182, no. 3, pp. 459-465. https://doi.org/10.1083/jcb.200803024
Medici, Damian ; Razzaque, Mohammed S. ; DeLuca, Stephelynn ; Rector, Trent L. ; Hou, Bo ; Kang, Kihwa ; Goetz, Regina ; Mohammadi, Moosa ; Kuro-o, Makoto ; Olsen, Bjorn R. ; Lanske, Beate. / FGF-23 - Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis. In: Journal of Cell Biology. 2008 ; Vol. 182, No. 3. pp. 459-465.
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AU - Hou, Bo

AU - Kang, Kihwa

AU - Goetz, Regina

AU - Mohammadi, Moosa

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