Medici, DamianRazzaque, Mohammed S.DeLuca, StephelynnRector, Trent L.Hou, BoKang, KihwaGoetz, ReginaMohammadi, MoosaKuro-o, MakotoOlsen, Bjorn R.Lanske, Beate2019-10-032008Medici, Damian, Mohammed S. Razzaque, Stephelynn DeLuca, Trent L. Rector, Bo Hou, Kihwa Kang, Regina Goetz, et al. 2008. “FGF-23–Klotho Signaling Stimulates Proliferation and Prevents Vitamin D–induced Apoptosis.” The Journal of Cell Biology 182 (3): 459–65. https://doi.org/10.1083/jcb.200803024.0021-95251540-8140http://nrs.harvard.edu/urn-3:HUL.InstRepos:41467426Fibroblast 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 1 alpha-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.en-USJournal Article2019-10-0310.1083/jcb.200803024