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

摘要

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 NF kappa B 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 NF kappa B. 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. NF kappa B 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 NF kappa B activity.