Salusin-β通过Nrf-2信号通路调控高糖诱导的HK-2细胞铁死亡的机制

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 (<em>Nrf‑2</em>) 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.