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Journal of endocrinological investigation
Dec, 2019;42 (12): 1477-1483.

p38MAPK controls fibroblast growth factor 23 (FGF23) synthesis in UMR106-osteoblast-like cells and in IDG-SW3 osteocytes.

F Ewendt, M Föller
Author Information
  1. F Ewendt: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
  2. M Föller: Institute of Physiology, University of Hohenheim, Garbenstraße 30, 70599, Stuttgart, Germany. michael.foeller@uni-hohenheim.de.
PMID: 31201665 DOI: 10.1007/s40618-019-01073-y

Abstract

BACKGROUND: p38 mitogen-activated protein kinase (p38MAPK) is a serine/threonine kinase activated by cellular stress stimuli including radiation, osmotic shock, and inflammation and influencing apoptosis, cell proliferation, and autophagy. Moreover, p38MAPK induces transcriptional activity of the transcription factor complex NFκB mediating multiple pro-inflammatory cellular responses. Fibroblast growth factor 23 (FGF23) is produced by bone cells, and regulates renal phosphate and vitamin D metabolism as a hormone. FGF23 expression is enhanced by NFκB. Here, we analyzed the relevance of p38MAPK activity for the production of FGF23.
METHODS: Fgf23 expression was analyzed by qRT-PCR and FGF23 protein by ELISA in UMR106 osteoblast-like cells and in IDG-SW3 osteocytes.
RESULTS: Inhibition of p38MAPK with SB203580 or SB202190 significantly down-regulated Fgf23 expression and FGF23 protein expression. Conversely, p38MAPK activator anisomycin increased the abundance of Fgf23 mRNA. NFκB inhibitors wogonin and withaferin A abrogated the stimulatory effect of anisomycin on Fgf23 gene expression.
CONCLUSION: p38MAPK induces FGF23 formation, an effect at least in part dependent on NFκB activity.

Keywords

Anisomycin Calcium Klotho NFκB Phosphate

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Grants

  1. Fo695/2-1/Deutsche Forschungsgemeinschaft

MeSH Term

Animals
Anisomycin
Cell Line
Enzyme Inhibitors
Fibroblast Growth Factor-23
Fibroblast Growth Factors
Flavanones
Gene Expression Regulation
Imidazoles
Mice
NF-kappa B
Osteoblasts
Osteocytes
Pyridines
Rats
Signal Transduction
Withanolides
p38 Mitogen-Activated Protein Kinases

Chemicals

Enzyme Inhibitors
Fgf23 protein, mouse
Fgf23 protein, rat
Flavanones
Imidazoles
NF-kappa B
Pyridines
Withanolides
Fibroblast Growth Factors
Anisomycin
Fibroblast Growth Factor-23
p38 Mitogen-Activated Protein Kinases
withaferin A
SB 203580
wogonin
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
Journal Article

Word Cloud

Created with Highcharts 10.0.0p38MAPKFGF23NFκBexpressionFgf23proteinactivityfactorcellskinasecellularinducesgrowth23analyzedIDG-SW3osteocytesanisomycineffectBACKGROUND:p38mitogen-activatedserine/threonineactivatedstressstimuliincludingradiationosmoticshockinflammationinfluencingapoptosiscellproliferationautophagyMoreovertranscriptionaltranscriptioncomplexmediatingmultiplepro-inflammatoryresponsesFibroblastproducedboneregulatesrenalphosphatevitaminDmetabolismhormoneenhancedrelevanceproductionMETHODS:qRT-PCRELISAUMR106osteoblast-likeRESULTS:InhibitionSB203580SB202190significantlydown-regulatedConverselyactivatorincreasedabundancemRNAinhibitorswogoninwithaferinabrogatedstimulatorygeneCONCLUSION:formationleastpartdependentcontrolsfibroblastsynthesisUMR106-osteoblast-likeAnisomycinCalciumKlothoPhosphate

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