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

98 Scopus citations

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

ASJC Scopus subject areas

  • Cell Biology

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    Medici, D., Razzaque, M. S., DeLuca, S., Rector, T. L., Hou, B., Kang, K., Goetz, R., Mohammadi, M., Kuro-o, M., Olsen, B. R., & 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