anisomycin and wogonin

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.. Fgf23 expression was analyzed by qRT-PCR and FGF23 protein by ELISA in UMR106 osteoblast-like cells and in IDG-SW3 osteocytes.. 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.. p38MAPK induces FGF23 formation, an effect at least in part dependent on NFκB activity.

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