Department of Physiology, University of Hohenheim, Garbenstraße 30, 70599, Stuttgart, Germany.
Mol Cell Biochem. 2022 Feb;477(2):363-370. doi: 10.1007/s11010-021-04287-y. Epub 2021 Nov 3.
Endocrine and paracrine fibroblast growth factor 23 (FGF23) is a protein predominantly produced by bone cells with strong impact on phosphate and vitamin D metabolism by targeting the kidney. Plasma FGF23 concentration early rises in kidney and cardiovascular diseases correlating with progression and outcome. Lactic acid is generated in anaerobic glycolysis. Lactic acidosis is the consequence of various physiological and pathological conditions and may be fatal. Since FGF23 production is stimulated by inflammation and lactic acid induces pro-inflammatory signaling, we investigated whether and how lactic acid influences FGF23. Experiments were performed in UMR106 osteoblast-like cells, Fgf23 mRNA levels estimated from quantitative real-time polymerase chain reaction, and FGF23 protein determined by enzyme-linked immunosorbent assay. Lactic acid dose-dependently induced Fgf23 gene expression and up-regulated FGF23 synthesis. Also, Na-lactate as well as formic acid and acetic acid up-regulated Fgf23. The lactic acid effect was significantly attenuated by nuclear factor kappa-light-chain enhancer of activated B-cells (NFκB) inhibitors wogonin and withaferin A. Lactic acid induces FGF23 production, an effect at least in part mediated by NFκB. Lactic acidosis may, therefore, be paralleled by a surge in plasma FGF23.
内分泌和旁分泌成纤维细胞生长因子 23（FGF23）主要由骨细胞产生，通过靶向肾脏对磷酸盐和维生素 D 代谢有强烈影响。血浆 FGF23 浓度在肾脏和心血管疾病早期升高，与疾病进展和结局相关。乳酸是无氧糖酵解产生的。乳酸酸中毒是各种生理和病理状况的结果，可能是致命的。由于 FGF23 的产生受炎症刺激，而乳酸诱导促炎信号，我们研究了乳酸是否以及如何影响 FGF23。实验在 UMR106 成骨样细胞中进行，通过定量实时聚合酶链反应估计 Fgf23 mRNA 水平，并通过酶联免疫吸附试验测定 FGF23 蛋白。乳酸呈剂量依赖性诱导 Fgf23 基因表达，并上调 FGF23 合成。此外，Na-乳酸以及甲酸和乙酸也上调了 Fgf23。核因子 kappa-轻链增强子的 B 细胞（NFκB）抑制剂白杨素和醉茄素 A 显著减弱了乳酸的作用。乳酸诱导 FGF23 的产生，其作用至少部分通过 NFκB 介导。因此，乳酸酸中毒可能伴随着血浆 FGF23 的激增。
