Red de Investigación Renal (REDinREN), 28029 Madrid, Spain.
Vascular and Renal Translational Research Group, Institut de Recerca Biomèdica de Lleida IRBLleida, 25198 Lleida, Spain.
Nutrients. 2022 Jun 22;14(13):2576. doi: 10.3390/nu14132576.
Increased FGF23 levels are an early pathological feature in chronic kidney disease (CKD), causing increased cardiovascular risk. The regulation of FGF23 expression is complex and not completely understood. Thus, Ca has been shown to induce an increase in FGF23 expression, but whether that increase is mediated by simultaneous changes in parathyroid hormone (PTH) and/or vitamin D is not fully known.
Osteoblast-like cells (OLCs) from vitamin D receptor (VDR) and VDR mice were incubated with Ca for 18 h. Experimental hypercalcemia was induced by calcium gluconate injection in thyro-parathyroidectomized (T-PTX) VDR and VDR mice with constant PTH infusion.
Inorganic Ca induced an increase in FGF23 gene and protein expression in osteoblast-like cells (OLCs), but the increase was blunted in cells lacking VDR. In T-PTX VDR and VDR mice with constant PTH levels, hypercalcemia induced an increase in FGF23 levels, but to a lower extent in animals lacking VDR. Similar results were observed in FGF23 expression in bone. Renal and bone 1α-hydroxylase expression was also modulated.
Our study demonstrates that Ca can increase FGF23 levels independently of vitamin D and PTH, but part of the physiological increase in FGF23 induced by Ca is mediated by vitamin D signaling.
成纤维细胞生长因子 23（FGF23）水平升高是慢性肾脏病（CKD）的早期病理特征，可增加心血管风险。FGF23 表达的调节较为复杂，尚未完全阐明。因此，已有研究表明钙可诱导 FGF23 表达增加，但这种增加是否通过甲状旁腺激素（PTH）和/或维生素 D 的同时变化介导尚不完全清楚。
用钙孵育维生素 D 受体（VDR）和 VDR 小鼠的成骨细胞样细胞（OLC）18 小时。通过向甲状腺-甲状旁腺切除（T-PTX）VDR 和 VDR 小鼠中注射葡萄糖酸钙诱导实验性高钙血症，并持续输注 PTH。
无机钙可诱导成骨细胞样细胞（OLC）中 FGF23 基因和蛋白表达增加，但缺乏 VDR 的细胞中增加幅度较小。在 T-PTX VDR 和 VDR 小鼠中，在 PTH 水平恒定的情况下，高钙血症可诱导 FGF23 水平升高，但在缺乏 VDR 的动物中升高幅度较小。在骨中也观察到 FGF23 表达的类似结果。肾和骨 1α-羟化酶的表达也受到调节。
本研究表明，钙可增加 FGF23 水平，而不依赖于维生素 D 和 PTH，但钙诱导的 FGF23 生理增加的一部分是通过维生素 D 信号介导的。
