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

• Published in: Molecular medicine reports Vol. 24; no. 3
• Main Authors: Wang, Wen-Juan, Jiang, Xia, Gao, Chang-Chun, Chen, Zhi-Wei
• Format: Journal Article
• Language: English
• Published: Athens Spandidos Publications UK Ltd 01-09-2021; D.A. Spandidos
• Subjects: Antibodies; Antioxidants; Apoptosis; Biotechnology; Buthionine sulfoximine; Cell culture; Diabetes; Diabetes mellitus; Diabetic nephropathy; Ferroptosis; GA-binding protein; Glucose; Kidney diseases; Kidneys; Lipid peroxidation; Membranes; Nephropathy; Oxidative stress; Pathogenesis; Penicillin; Proteins; Reactive oxygen species
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2021.12313

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.