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Abstract: SA-PO428

IL-6-ZIP14-GPX4 Axis Is Involved in Ferroptosis in Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Wu, Keping, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Xu, Xiaochang, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Zhu, Enyi, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Dong, Yejing, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Zhang, Yimin, Sun Yat-Sen University, Guangzhou, Guangdong, China
Background

Ferroptosis is caused by lipid peroxidation and iron accumulation. Our previous study have shown that ZIP14 is involved in ferroptosis in Diabetic kidney disease(DKD), but the mechanism is unknown. Interleukin-6 (IL-6) can specifically increase the expression of ZIP14. Thus, we hypothesize that IL-6-ZIP14-GPX4 axis is involved in ferroptosis in DKD.

Methods

Renal biopsies of patients with DKD were collected to detect the changes related to ferroptosis. We induced DKD in 8-week-old male rats with streptozotocin (STZ) and treated with GPX4-Adeno-associated viral (AAV) via tail vein to analyze the degree of renal injury. The expression of GPX4, IL-6 and ZIP14 was detecetd in kidney.

Results

The expression of GPX4 was down-regulated in DKD. While the levels of IL-6 and ZIP14 were up-regulated in kidney of STZ rats. Iron deposition was confirmed in kidney of DKD. The mitochondria of renal biopsy presented reduced mitochondrial volume and missing mitochondrial cristae. The levels of malondialdehyde (MDA), and Fe2+ in STZ group were higher than in the control. While the levels of GSH and SOD were lower than in the control. Over-expression of GPX4 decreased the expression of IL-6 and ZIP14 in kidney of STZ rats. Also, the urine protein-creatinine ratio, and the levels of both MDA and Fe2+ were decreased.

Conclusion

The IL-6-ZIP14-GPX4 axis is involved in ferroptosis in DKD.