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

作者：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^*

来源：The Journal of Cell Biology, 2008, 182(3): 459-465.

DOI：10.1083/jcb.200803024

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 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.

• 出版日期2008-8-11