Pathophysiological Mechanisms of Diabetic Nephropathy: Role of S1R/Nrf2 Antioxidant Axis

Abstract

Diabetic nephropathy (DN) stands out as one of the most significant complications of diabetes mellitus, and it is a primary contributor to end-stage kidney disease globally. The progression of DN is complex, involving intricate interplays, including oxidative stress, inflammation, fibrosis, and cellular apoptosis. Recently, scientific investigations have emphasized the significant role of the sigma-1 receptor (S1R) and nuclear factor erythroid 2-related factor 2 (Nrf2) in mitigating these detrimental effects. Scientific evidence indicated that the activation of S1R could effectively diminish cellular oxidative stress, inflammation, and cell death, alleviating renal damage in diabetic nephropathy. Nrf2, a key regulator of antioxidant responses, protects renal cells from oxidative injury and modulates inflammatory responses. Targeting S1R and Nrf2 may provide novel therapeutic approaches for managing diabetic nephropathy. This review offers a detailed overview of the pathophysiological mechanisms underlying DN, focusing on the S1R/Nrf2 axis and its potential as a promising therapeutic target for diabetic nephropathy.