Abstract
Epidemiological investigations have shown an elevated expression of fibroblast growth factor 21 (FGF21) in the serum of patients with hyperuricemia. However, the effect of FGF21 on hyperuricemic nephropathy is still unknown. The purpose of this study, therefore, was to explore the effect and mechanism of action of FGF21 on hyperuricemic nephropathy. The level of FGF21 in PBMCs was determined in 10 patients with hyperuricemic nephropathy. Hyperuricemic mice models were induced in wild-type C57BL/6 and FGF21 knockout mice. Six mice in each group were treated with FGF21 at a dose of 1mg/kg and 5mg/kg for 30 days. For the in vitro studies, glomerular mesangial cells were exposed to lipopolysaccharide and monosodium uric acid to induce inflammation. This was followed by treatment with 100nM, 1000nM of FGF21 for 72 h to observe the therapeutic effect. The levels of FGF21 in patients with hyperuricemic nephropathy were elevated. Also, FGF21 knockout mice experienced more severe nephropathy compared to the WT mice. This was characterized by an increase in inflammatory factors and fibrosis in the kidney, which was reversed by exogenous FGF21 treatment. FGF21 recorded a significant therapeutic effect through the activation of Akt/Nrf2 signal pathway in both in vivo and in vitro studies. However, the effect increasing effect of FGF21 on Nrf2 was reduced by the addition of Akt inhibitor GSK690693. In conclusion, our study found for the first time that FGF21 can significantly improve hyperuricemic nephropathy through the promotion of the Akt/Nrf2 signalling pathway leading to improvement in oxidative stress.
Aryl hydrocarbon receptor-fibroblast growth factor 21 dissociation of fatty liver from insulin resistance: A timely matter?
