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

  • F. Ewendt
  • M. FöllerEmail author
Original Article

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 NFκB Calcium Phosphate Klotho 

Notes

Acknowledgements

The authors acknowledge the technical assistance of S. Ross and F. Reipsch.

Funding

This study was supported by the Deutsche Forschungsgemeinschaft [Fo 695/2-1].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Informed consent is not required in this type of study.

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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  1. 1.Institute of Agricultural and Nutritional SciencesMartin Luther University Halle-WittenbergHalle (Saale)Germany
  2. 2.Institute of PhysiologyUniversity of HohenheimStuttgartGermany

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