Journal Article

A potential link between fibroblast growth factor-23 and the progression of AKI to CKD

Tang, Rong, Lu, Yinghui, Xu, Shutian, Han, Cui, Zheng, Chunxia

2023

Overview

Background 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. Method 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. Results 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. Conclusion 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acute Kidney Injury - blood / Adult / AKI – CKD / Analysis / Animals / Antibodies / Biotechnology / Case-Control Studies / Cell Line / Chronic kidney failure / Collagen (type I) / Correlation analysis / Disease Progression / Enzyme-linked immunosorbent assay / Female / FGF-23 / Fibroblast growth factor 23 / Fibroblast growth factor receptors / Fibroblast Growth Factor-23 - blood / Fibroblast growth factors / Fibroblasts / Fibrosis / Forecasts and trends / Growth factors / Humans / Immunoblotting / Immunofluorescence / Internal Medicine / Ischemia / Kidney - pathology / Kidney diseases / Male / Medical prognosis / Medicine / Medicine & Public Health / Mice / Mice, Inbred C57BL / Middle Aged / Mortality / Nephrology / Patients / Prevention / Regression analysis / Renal fibrosis / Renal Insufficiency, Chronic - blood / Reperfusion / Risk factors / Smad protein / Smad3 protein / Transforming growth factor-b / Transforming growth factors / Wnt protein / β-Catenin