Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
Institute of Physiology, University of Hohenheim, Garbenstraße 30, 70599, Stuttgart, Germany.
J Endocrinol Invest. 2019 Dec;42(12):1477-1483. doi: 10.1007/s40618-019-01073-y. Epub 2019 Jun 14.
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.
p38 丝裂原活化蛋白激酶（p38MAPK）是一种丝氨酸/苏氨酸激酶，可被细胞应激刺激物激活，包括辐射、渗透压冲击和炎症，并影响细胞凋亡、细胞增殖和自噬。此外，p38MAPK 诱导转录因子复合物 NFκB 的转录活性，介导多种促炎细胞反应。成纤维细胞生长因子 23（FGF23）由骨细胞产生，作为一种激素调节肾脏磷酸盐和维生素 D 代谢。FGF23 的表达受 NFκB 增强。在这里，我们分析了 p38MAPK 活性对 FGF23 产生的相关性。
通过 qRT-PCR 分析 UMR106 成骨样细胞和 IDG-SW3 骨细胞中的 Fgf23 表达，通过 ELISA 分析 FGF23 蛋白。
用 SB203580 或 SB202190 抑制 p38MAPK 显著下调了 Fgf23 的表达和 FGF23 蛋白的表达。相反，p38MAPK 激活剂anisomycin 增加了 Fgf23 mRNA 的丰度。NFκB 抑制剂 wogonin 和 withaferin A 阻断了 anisomycin 对 Fgf23 基因表达的刺激作用。
p38MAPK 诱导 FGF23 的形成，这种作用至少部分依赖于 NFκB 活性。
