1. Academic Validation
  2. Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism

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

  • Mol Med. 2021 Nov 13;27(1):147. doi: 10.1186/s10020-021-00408-x.
Hua-Chun Weng 1 Xin-Yu Lu 2 Yu-Peng Xu 2 Yi-Hong Wang 3 Dan Wang 3 Yi-Ling Feng 3 Zhang Chi 4 Xiao-Qing Yan 4 Chao-Sheng Lu 5 Hong-Wei Wang 6
Affiliations

Affiliations

  • 1 The College of Medical Technology, Shanghai University of Medicine & Health Sciences, Shanghai, 200000, China.
  • 2 The First Clinical Medical College of Wenzhou Medical University, Wenzhou, 325000, China.
  • 3 Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, 322 Nanbaixiang Street, Wenzhou, 325000, Zhejiang, China.
  • 4 Ruian Center of Chinese-American Research Institute for Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 5 Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, 322 Nanbaixiang Street, Wenzhou, 325000, Zhejiang, China. lucs363@163.com.
  • 6 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, 322 Nanbaixiang Street, Wenzhou, 325000, Zhejiang, China. 15258085168@163.com.
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.

Keywords

AMPK; Fibroblast growth factor 21; Hypertension; Renal injury.

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