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Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a Nrf‑2‑dependent manner

  • Authors:
    • Wen-Juan Wang
    • Xia Jiang
    • Chang-Chun Gao
    • Zhi-Wei Chen
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Center of Blood Purification, The Second People's Hospital of Nantong, Nantong, Jiangsu 226002, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 674
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    Published online on: July 22, 2021
       https://doi.org/10.3892/mmr.2021.12313
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Abstract

Ferroptosis is critically involved in the pathophysiology of diabetic nephropathy (DN). As a bioactive peptide, salusin‑β is abundantly expressed in the kidneys. However, it is unclear whether salusin‑β participates in the pathologies of diabetic kidney damage by regulating ferroptosis. The present study found that high glucose (HG) treatment upregulated the protein expressions of salusin‑β in a dose‑ and time‑dependent manner. Genetic knockdown of salusin‑β retarded, whereas overexpression of salusin‑β aggravated, HG‑triggered iron overload, antioxidant capability reduction, massive reactive oxygen species production and lipid peroxidation in HK‑2 cells. Mechanistically, salusin‑β inactivated nuclear factor erythroid‑derived 2‑like 2 (Nrf‑2) signaling, thus contributing to HG‑induced ferroptosis‑related changes in HK‑2 cells. Notably, the protein expression of salusin‑β was upregulated by ferroptosis activators, such as erastin, RSL3, FIN56 and buthionine sulfoximine. Pretreatment with ferrostatin‑1 (a ferroptosis inhibitor) prevented the upregulated protein expression of salusin‑β in HK‑2 cells exposed to HG. Taken together, these results suggested that a positive feedback loop between salusin‑β and ferroptosis primes renal tubular cells for injury in diabetes.
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Copy and paste a formatted citation
Spandidos Publications style
Wang W, Jiang X, Gao C and Chen Z: Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a <em>Nrf‑2</em>‑dependent manner. Mol Med Rep 24: 674, 2021.
APA
Wang, W., Jiang, X., Gao, C., & Chen, Z. (2021). Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a <em>Nrf‑2</em>‑dependent manner. Molecular Medicine Reports, 24, 674. https://doi.org/10.3892/mmr.2021.12313
MLA
Wang, W., Jiang, X., Gao, C., Chen, Z."Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a <em>Nrf‑2</em>‑dependent manner". Molecular Medicine Reports 24.3 (2021): 674.
Chicago
Wang, W., Jiang, X., Gao, C., Chen, Z."Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a <em>Nrf‑2</em>‑dependent manner". Molecular Medicine Reports 24, no. 3 (2021): 674. https://doi.org/10.3892/mmr.2021.12313
Copy and paste a formatted citation
x
Spandidos Publications style
Wang W, Jiang X, Gao C and Chen Z: Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a <em>Nrf‑2</em>‑dependent manner. Mol Med Rep 24: 674, 2021.
APA
Wang, W., Jiang, X., Gao, C., & Chen, Z. (2021). Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a <em>Nrf‑2</em>‑dependent manner. Molecular Medicine Reports, 24, 674. https://doi.org/10.3892/mmr.2021.12313
MLA
Wang, W., Jiang, X., Gao, C., Chen, Z."Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a <em>Nrf‑2</em>‑dependent manner". Molecular Medicine Reports 24.3 (2021): 674.
Chicago
Wang, W., Jiang, X., Gao, C., Chen, Z."Salusin‑β participates in high glucose‑induced HK‑2 cell ferroptosis in a <em>Nrf‑2</em>‑dependent manner". Molecular Medicine Reports 24, no. 3 (2021): 674. https://doi.org/10.3892/mmr.2021.12313
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