Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism

Abstract

Background Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. Methods Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. 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. 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. Results We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. Conclusion These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

FGF21 inhibited NETs formation induced by myocardial I/R injury via AMPK

“…In hypertensive and diabetic mice models, the absence of FGF21 resulted in a pronounced exacerbation of in ammatory response and oxidative stress. Conversely, administration of FGF21 signi cantly alleviated these conditions by promoting the phosphorylation of AMPK, highlighting the crucial role of FGF21 in mitigating in ammatory and oxidative stress pathways [31,32]. Subsequent investigations have unveiled that FGF21 exerts its anti-in ammatory, antioxidant stress, and inhibitory effects on myocardial remodeling and apoptosis through two distinct pathways.…”

Influence of Hypersensitive C-Reactive Protein on the Effect of Continuous Antihypertensive Pharmacological Therapy

“…Furthermore, inhibition of individual cytokines and use of immunosuppressive drugs may prevent or ameliorate experimental hypertension and reduce hypertensive organ injury. 8,26 Research has shown that elevated BP may result from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. 14,27–29 Antihypertensive therapy can reduce hsCRP levels, relieve the systemic chronic inflammatory response, and thus may partly alleviate the adverse effects of inflammation on target organs.…”

“…[2][3][4][5] Although the 5 major antihypertensive drug classes recommended in the current hypertension management guidelines have been associated with reduced blood pressure (BP) and cardiovascular and cerebrovascular events, 6,7 the hypertension control rate remains unsatisfactory in many areas around the world. 8 One of the reasons for this may be the lack of effective indicators to guide individualized treatment.…”

Bioactive Peptides from Ruditapes philippinarum Attenuate Hypertension and Cardiorenal Damage in Deoxycorticosterone Acetate–Salt Hypertensive Rats

“…Persistent hypertension has been shown to contribute to kidney damage [16,17]. HE staining kidney sections from the Mod group revealed inflammatory cell infiltration; renal glomerular hypertrophy and higher cell numbers; the compensatory dilatation of renal tubules; and the flattening and detachment of epithelial cells, indicating renal injury (Figure 5A).…”