Fibroblast Growth Factor 21 Ameliorates Hyperuricemic Nephropathy By Improving Oxidative Stress Through Activating Akt/Nrf2 Signaling Pathway

Abstract Epidemiological investigations have shown an elevated expression of circulating fibroblast growth factor 21 (FGF21) of patients with hyperuricemia. However, the effect of FGF21 on hyperuricemic nephropathy (HN) is still unknown. The purpose of this study, therefore, was to explore the effect and mechanism of action of FGF21 on HN. The level of FGF21 in peripheral blood mononuclear cells (PBMCs) was determined in 10 patients with HN. In vivo models of HN were induced in C57BL/6 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 (GMCs) were exposed to lipopolysaccharide and monosodium uric acid to induce inflammation and oxidative stress. 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 HN were elevated. Also, we found that exogenous injection of FGF21 could significantly improve kidney injury in HN mice. This was characterized by a decrease in inflammatory factors and fibrosis and the improvement of oxidative stress. FGF21 recorded a significant therapeutic effect through the activation of Nrf2 in both in vivo and in vitro studies. However, the effect of enhancement 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 HN through the promotion of the Akt/Nrf2 signalling pathway leading to improvement in oxidative stress.