Abstract
Acute kidney injury (AKI) is a common complication in cancer patients. Kidney function is closely related to patients’ quality of life and tumor prognosis. Cisplatin is a highly effective anti-tumor drug. However, the use of cisplatin is limited by its nephrotoxicity. It has been reported that FGF21 has a renal-protective function, but the mechanisms by which it does so remain unclear. In this study, we show that the expression of FGF21 is significantly upregulated in both in vitro and in vivo cisplatin-induced AKI models. Administration of recombinant FGF21 to cisplatin-induced AKI mice resulted in significantly decreased blood urea nitrogen (BUN) and serum creatinine levels, as well as significantly reduced protein levels of kidney injury molecule-1 (TIM-1), C-caspase 3, and Bax. H&E-stained kidney sections from cisplatin-induced AKI mice treated with recombinant FGF21 showed a relatively normal renal tissue structure, a reduced number of necrotic sites and vacuolar changes, and decreased casts, suggesting alleviated renal tubular injury. Experiments with an AKI cell model (cisplatin-treated HK-2 cells) yielded similar results as the mouse model; recombinant FGF21 significantly downregulated protein expression levels of TIM-1, C-caspase 3, and Bax. Furthermore, administration of recombinant FGF21 to cisplatin-treated AKI models significantly increased SIRT1 expression, and the beneficial effects of FGF21 on kidney injury were reversed by SIRT1 knockdown. Collectively, our results suggest that SIRT1 mediates the protective effect of FGF21 on cisplatin-induced kidney injury.
Highlights
Acute kidney injury (AKI) is a clinical syndrome characterized by an abrupt decline in kidney function, a decrease in glomerular filtration rate, and the accumulation of nitrogenous waste in the kidney (Vanmassenhove et al, 2017)
As for in vivo experiments in mice, we found that both blood urea nitrogen (BUN) levels and serum creatinine levels began to rise 24 h after cisplatin treatment, reaching a maximum at 72 h
To determine whether recombinant human FGF21 (rhFGF21) prevents cisplatin-induced AKI by activating SIRT1, we examined the function of rhFGF21 in HK-2 cells after SIRT1 knockdown
Summary
Acute kidney injury (AKI) is a clinical syndrome characterized by an abrupt decline in kidney function, a decrease in glomerular filtration rate, and the accumulation of nitrogenous waste in the kidney (Vanmassenhove et al, 2017). Many factors contribute to the induction of AKI, including drugs, hypovolemia, sepsis, and surgical injury (Motwani et al, 2018). AKI is widely distributed among clinical departments (Basile et al, 2016). AKI incidence has reached 5–7% and is still rising, with a mortality rate of 40%. AKI is important risk factor for the development of chronic kidney disease (Coca et al, 2012; Oh et al, 2017)
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