However, the molecular mechanism of the etiology of salt-sensitive hypertensive nephropathy (SSHN) is not clear and no effective treatment has been developed.ДЇibroblast growth factor 21 (FGF21), a member of the FGF superfamily, is widely expressed in liver, adipose tissue, pancreas and other metabolic organs and plays metabolic regulatory roles in form of endocrine (Tezze et al. Furthermore, studies have shown that patients with salt-sensitive hypertension tend to have more severe kidney damage and a higher rate of development of end-stage kidney disease (Slagman et al. Once patients develop end-stage renal disease, undergoing dialysis and kidney transplantation are only ways (Hart and Bakris 2010). To date, the treatment of hypertensive nephropathy is limited, such as controlling blood pressure and regulating living habits. Hypertension is the main risk factor for chronic kidney disease and one of the most common causes of renal failure (Gargiulo et al. About 60% of patients with hypertension are sensitive to salt accompanied with uncontrollable blood pressure and serious complications (Rust and Ekmekcioglu 2017). SSHT is the most common type of hypertension in clinic. Elevated blood pressure with relatively high salt intake is defined as salt-sensitive hypertension (SSHT) (Abais-Battad et al. High salt intake is one of the important environmental factors, which is closely related to the occurrence and development of hypertension (Hirohama and Fujita 2019). Hypertension is an imbalance in the regulation of normal blood pressure caused by the interaction of polygenetic inheritance and multiple environmental factors, which has become a serious public health problem affecting 30% of adults around the world (Fatani et al. These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-ОєB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. MethodsД¬hanges of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment.

Image pro plus hematoxylin and eosin