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bioRxiv · 10.1101/520254

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

Bär, L.·Hase, P.·Föller, M.
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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 NF{kappa}B, 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, Go6976, sotrastaurin and ruboxistaurin supressed Fgf23 gene expression. NF{kappa}B 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 NF{kappa}B.

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Bär, L., Hase, P., Föller, M.. 2019-01-14. PKC regulates the production of fibroblast growth factor 23 (FGF23). https://doi.org/10.1101/520254

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