Nephrology Department, Dongguan People's Hospital Affiliated to Southern Medical University, Dongguan, Guangdong 523059, P.R. China.
Int J Mol Med. 2020 Nov;46(5):1783-1793. doi: 10.3892/ijmm.2020.4719. Epub 2020 Sep 4.
Phosphorus reduction can prevent against vascular calcification (VC) in chronic kidney disease (CKD), but the mechanisms underlying its actions remain unclear. The aim of the present study was to determine the effect of a fortified phosphorus‑lowing treatment on VC in CKD. Serum levels of creatinine, blood urea nitrogen (BUN), fibroblast growth factor 23 (FGF23), calcium and phosphorus, and the plasma levels of parathyroid hormone (PTH) were determined in an animal model of CKD treated with or without lanthanum. Haematoxylin and eosin (H&E) staining was performed to examine the structure of kidney tissues. Western blot analysis was performed to compare the levels of total‑ (t‑) extracellular signal‑related kinase (ERK) and phospho‑ (p‑)ERK among the different experimental groups to investigate the effect of FGF23 on p‑ERK expression. In the animal model, administration of adenine increased the serum levels of creatinine, BUN, FGF23 and phosphorus but decreased the serum levels of calcium. In addition, adenine treatment increased the plasma levels of PTH. H&E staining showed that lanthanum treatment did not alter the severity of renal cortex injury. Furthermore, the levels of t‑ERK levels did not notably differ between the Adenine‑free, Adenine‑vehicle and Adenine‑lanthanum groups, whereas the levels of p‑ERK and aortic calcium in the Adenine‑vehicle group were significantly upregulated. In addition, ectopic overexpression of FGF23 increased the levels of p‑ERK, Msx2 and Osx in a dose‑dependent manner. Furthermore, a total of 48 patients were enrolled in the present study. In the fortified group, the serum levels of FGF23, phosphorus and PTH were significantly reduced, whereas the serum levels of calcium were significantly increased, indicating an enhanced preventative effect in the fortified group. The results of the present study suggest that FGF23 may be used as a therapeutic target in the management and prevention of VC in CKD.
磷的减少可以预防慢性肾脏病（CKD）中的血管钙化（VC），但其作用机制尚不清楚。本研究旨在确定强化降磷治疗对 CKD 中 VC 的影响。在 CKD 动物模型中用或不用镧处理后，测定血清肌酐、血尿素氮（BUN）、成纤维细胞生长因子 23（FGF23）、钙和磷水平，以及血浆甲状旁腺激素（PTH）水平。通过苏木精和伊红（H&E）染色观察肾组织结构。通过 Western blot 分析比较不同实验组中总（t）细胞外信号调节激酶（ERK）和磷酸化（p）ERK 的水平，以研究 FGF23 对 p-ERK 表达的影响。在动物模型中，腺嘌呤给药增加了血清肌酐、BUN、FGF23 和磷水平，但降低了血清钙水平。此外，腺嘌呤处理增加了血浆 PTH 水平。H&E 染色显示，镧处理并未改变肾皮质损伤的严重程度。此外，Adenine-free、Adenine-vehicle 和 Adenine-lanthanum 组之间 t-ERK 水平无明显差异，而 Adenine-vehicle 组 p-ERK 和主动脉钙水平明显上调。此外，FGF23 的异位过表达以剂量依赖性方式增加了 p-ERK、Msx2 和 Osx 的水平。此外，本研究共纳入 48 例患者。在强化组中，FGF23、磷和 PTH 血清水平显著降低，而钙血清水平显著升高，表明强化组的预防效果增强。本研究结果表明，FGF23 可用作 CKD 中 VC 管理和预防的治疗靶点。
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