Jinling Hospital, National Clinical Research Center of Kidney Diseases, Nanjing University School of Medicine, Nanjing, China.
BMC Nephrol. 2023 Apr 4;24(1):87. doi: 10.1186/s12882-023-03125-1.
Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear.
Serum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFβ/Smad and Wnt/β-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis.
The level of serum FGF-23 was significantly different between AKI patients and healthy controls (P < 0.01). Moreover, serum FGF-23 levels in the CKD progression group were significantly higher than those in the non-CKD progression group of AKI patients (P < 0.01). In the AKI-CKD mouse model, serum FGF-23 levels were increased, and renal fibrosis occurred; moreover, the protein expression of β-catenin and p-Smad3 was upregulated. PD173074 downregulated the expression of β-catenin and p-Smad3 and reduced fibrosis in both mice and HK2 cells.
The increase in FGF-23 may be associated with the progression of AKI to CKD and may mediate renal fibrosis via TGF-β and Wnt/β-catenin activation.
急性肾损伤（AKI）患者在大约 10 年的随访后，发生慢性肾脏病（CKD）的风险增加 25%，死亡率增加 50%。成纤维细胞生长因子 23（FGF-23）在 AKI 早期发展时显著增加，在 CKD 患者中显著升高，并已成为 CKD 不良临床预后的主要生物标志物。然而，FGF-23 水平与 AKI 向 CKD 进展之间的潜在联系仍不清楚。
采用 ELISA 法检测 AKI 患者和缺血再灌注损伤（IRI）小鼠的血清 FGF-23 水平。用 FGF-23 和 FGFR 阻滞剂 PD173074 孵育培养的 HK2 细胞，然后用免疫荧光和免疫印迹法检测 TGFβ/Smad 和 Wnt/β-catenin。采用实时定量聚合酶链反应检测 COL1A1 和 COL4A1 的表达。组织学染色证实了肾纤维化。
AKI 患者和健康对照组之间的血清 FGF-23 水平差异有统计学意义（P<0.01）。此外，AKI 患者 CKD 进展组的血清 FGF-23 水平明显高于非 CKD 进展组（P<0.01）。在 AKI-CKD 小鼠模型中，血清 FGF-23 水平升高，发生肾纤维化，β-catenin 和 p-Smad3 蛋白表达上调。PD173074 下调了β-catenin 和 p-Smad3 的表达，减少了小鼠和 HK2 细胞的纤维化。
FGF-23 的增加可能与 AKI 向 CKD 的进展有关，并可能通过 TGF-β 和 Wnt/β-catenin 激活介导肾纤维化。
