Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis

Abstract

Glomerular podocyte damage is considered to be one of the main mechanisms leading to Diabetic nephropathy. 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(kidney cells) injury induced by high glucose (HG). As a result, cells with high glucose levels had increased cell viability and lower mortality. Prdx6 gene also reduces antioxidative stress.

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.

Conclusion: neuropathy kidney damage can be prevented by Sp1-mediated upregulation of Prdx6 gene expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and activated cell death mechanisms, which may provide new insights for the study of the mechanism of Diabetic nephropathy. Such a treatment can be realised through gene therapy.

Source ScienceDirect