erastin and Diabetic-Nephropathies

Glomerular podocyte damage is considered to be one of the main mechanisms leading to Diabetic nephropathy (DN). However, the relevant mechanism of podocyte injury is not yet clear. This study aimed to investigate the effect of peroxiredoxin 6 (Prdx6) on the pathogenesis of podocyte injury induced by high glucose (HG). The mouse glomerular podocyte MPC5 was stimulated with 30 nM glucose, and the Prdx6 overexpression vector or specificity protein 1 (Sp1) overexpression vector was transfected into MPC5 cells before the high glucose stimulation. As results, HG treatment significantly reduced the expression of Prdx6 and Sp1 in MPC5 cells. Prdx6 overexpression increased cell viability, while inhibited podocyte death, inflammation and podocyte destruction in HG-induced MPC5 cells. Prdx6 overexpression inhibited HG-induced ROS and MDA production, while restored SOD and GSH activity in MPC5 cells. Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. The improvement effect of Prdx6 on HG-induced podocyte damage could be eliminated by erastin. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Silencing Sp1 could eliminate the effect of Prdx6 on HG-induced podocyte damage. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced DN mice. Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis, which may provide new insights for the study of the mechanism of DN.

Topics: Animals; Apoptosis; Cell Line; Cell Survival; Diabetic Nephropathies; Epithelial Cells; Ferroptosis; Gene Expression Regulation; Glucose; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Peroxiredoxin VI; Piperazines; Podocytes; Reactive Oxygen Species; Signal Transduction; Sp1 Transcription Factor; Transcriptional Activation

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 (

Topics: Buthionine Sulfoximine; Carbolines; Cell Line; Diabetic Nephropathies; Ferroptosis; Glucose; Humans; Intercellular Signaling Peptides and Proteins; Lipid Peroxidation; NF-E2-Related Factor 2; Oximes; Piperazines; Reactive Oxygen Species; Signal Transduction; Sulfonamides; Up-Regulation