PKC regulates the production of fibroblast growth factor 23 (FGF23).
Animals
Cell Differentiation
/ drug effects
Cell Line
Fibroblast Growth Factors
/ genetics
NF-kappa B
/ antagonists & inhibitors
Osteoblasts
/ metabolism
Osteocytes
/ metabolism
Phosphates
/ metabolism
Protein Kinase C
/ antagonists & inhibitors
Protein Kinase Inhibitors
/ pharmacology
Proto-Oncogene Proteins c-akt
/ metabolism
Rats
Tetradecanoylphorbol Acetate
/ pharmacology
Up-Regulation
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
01
2019
accepted:
14
03
2019
entrez:
29
3
2019
pubmed:
29
3
2019
medline:
7
1
2020
Statut:
epublish
Résumé
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 osteoblast-like cells and in IDG-SW3 osteocytes, and FGF23 protein was measured by ELISA. Phorbol ester 12-O-tetradecanoylphorbol-13-acetate (PMA), a PKC activator, up-regulated FGF23 production. In contrast, PKC inhibitors calphostin C, Gö6976, sotrastaurin and ruboxistaurin suppressed FGF23 formation. 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.
Identifiants
pubmed: 30921339
doi: 10.1371/journal.pone.0211309
pii: PONE-D-19-00877
pmc: PMC6438472
doi:
Substances chimiques
Fgf23 protein, rat
0
NF-kappa B
0
Phosphates
0
Protein Kinase Inhibitors
0
Fibroblast Growth Factors
62031-54-3
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Protein Kinase C
EC 2.7.11.13
Tetradecanoylphorbol Acetate
NI40JAQ945
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0211309Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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