PKC regulates the production of fibroblast growth factor 23 (FGF23)

Abstract

Serine/threonine protein kinase C (PKC) is activated by diacylglycerol that is released from membrane lipids by phospholipase C in response to activation of G protein-coupled receptors or receptor tyrosine kinases. PKC isoforms are particularly relevant for proliferation and differentiation of cells including osteoblasts. Osteoblasts/osteocytes produce fibroblast growth factor 23 (FGF23), a hormone regulating renal phosphate and vitamin D handling. PKC activates NFκB, a transcription factor complex controlling FGF23 expression. Here, we analyzed the impact of PKC on FGF23 synthesis. Fgf23 expression was analyzed by qRT-PCR in UMR106 osteoblastlike cells and in IDG-SW3 osteocytes. Phorbol ester 12-O-tetradecanoylphorbol-13-acetate (PMA), a PKC activator, up-regulated Fgf23 expression. In contrast, PKC inhibitors calphostin C, Gö6976, sotrastaurin and ruboxistaurin supressed Fgf23 gene expression. NFκB inhibitor withaferin A abolished the stimulatory effect of PMA on Fgf23. PKC is a powerful regulator of FGF23 synthesis, an effect which is at least partly mediated by NFκB.

Relationship between GFR, intact PTH, oxidized PTH, non‐oxidized PTH as well as FGF23 in patients with CKD

“…UMR106 rat osteoblast‐like cells (ATCC, CRL‐1661) were cultured in Dulbecco's Modified Eagle Medium (DMEM) high glucose (Gibco, Life Technologies, Darmstadt, Germany) supplemented with 10% FBS (Gibco, Life Technologies) and 100 U/mL penicillin/100 μg/mL streptomycin (Gibco, Life Technologies) under standard culture conditions as described by Bär et al recently 19. Cells were first grown for 24 hours and then treated with or without the different PTH 1‐34 derivatives as indicated for additional 24 hours.…”