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 language | English (US) |
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Pages (from-to) | 459-465 |
Number of pages | 7 |
Journal | Journal of Cell Biology |
Volume | 182 |
Issue number | 3 |
DOIs | |
State | Published - Aug 11 2008 |
ASJC Scopus subject areas
- Cell Biology