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 diab...

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Autores principales:	Hua-Chun Weng, Xin-Yu Lu, Yu-Peng Xu, Yi-Hong Wang, Dan Wang, Yi-Ling Feng, Zhang Chi, Xiao-Qing Yan, Chao-Sheng Lu, Hong-Wei Wang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Hypertension Renal injury Fibroblast growth factor 21 AMPK Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/42f916f3a833486b840d8b7c6447bf5d
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spelling	oai:doaj.org-article:42f916f3a833486b840d8b7c6447bf5d2021-11-14T12:12:03ZFibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism10.1186/s10020-021-00408-x1076-15511528-3658https://doaj.org/article/42f916f3a833486b840d8b7c6447bf5d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s10020-021-00408-xhttps://doaj.org/toc/1076-1551https://doaj.org/toc/1528-3658Abstract 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.Hua-Chun WengXin-Yu LuYu-Peng XuYi-Hong WangDan WangYi-Ling FengZhang ChiXiao-Qing YanChao-Sheng LuHong-Wei WangBMCarticleHypertensionRenal injuryFibroblast growth factor 21AMPKTherapeutics. PharmacologyRM1-950BiochemistryQD415-436ENMolecular Medicine, Vol 27, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hypertension Renal injury Fibroblast growth factor 21 AMPK Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436
spellingShingle	Hypertension Renal injury Fibroblast growth factor 21 AMPK Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436 Hua-Chun Weng Xin-Yu Lu Yu-Peng Xu Yi-Hong Wang Dan Wang Yi-Ling Feng Zhang Chi Xiao-Qing Yan Chao-Sheng Lu Hong-Wei Wang Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism
description	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.
format	article
author	Hua-Chun Weng Xin-Yu Lu Yu-Peng Xu Yi-Hong Wang Dan Wang Yi-Ling Feng Zhang Chi Xiao-Qing Yan Chao-Sheng Lu Hong-Wei Wang
author_facet	Hua-Chun Weng Xin-Yu Lu Yu-Peng Xu Yi-Hong Wang Dan Wang Yi-Ling Feng Zhang Chi Xiao-Qing Yan Chao-Sheng Lu Hong-Wei Wang
author_sort	Hua-Chun Weng
title	Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism
title_short	Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism
title_full	Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism
title_fullStr	Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism
title_full_unstemmed	Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism
title_sort	fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism
publisher	BMC
publishDate	2021
url	https://doaj.org/article/42f916f3a833486b840d8b7c6447bf5d
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Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism

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