Signaling Pathways of Podocyte Injury in Diabetic Kidney Disease and the Effect of Sodium-Glucose Cotransporter 2 Inhibitors

Diabetic kidney disease (DKD) is one of the most important comorbidities for patients with diabetes, and its incidence has exceeded one tenth, with an increasing trend. Studies have shown that diabetes is associated with a decrease in the number of podocytes. Diabetes can induce apoptosis of podocytes through several apoptotic pathways or induce autophagy of podocytes through related pathways. At the same time, hyperglycemia can also directly lead to apoptosis of podocytes, and the related inflammatory reactions are all harmful to podocytes. Podocyte damage is often accompanied by the production of proteinuria and the progression of DKD. As a new therapeutic agent for diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to be effective in the treatment of diabetes and the improvement of terminal outcomes in many rodent experiments and clinical studies. At the same time, SGLT2i can also play a protective role in diabetes-induced podocyte injury by improving the expression of nephrotic protein defects and inhibiting podocyte cytoskeletal remodeling. Some studies have also shown that SGLT2i can play a role in inhibiting the apoptosis and autophagy of cells. However, there is no relevant study that clearly indicates whether SGLT2i can also play a role in the above pathways in podocytes. This review mainly summarizes the damage to podocyte structure and function in DKD patients and related signaling pathways, as well as the possible protective mechanism of SGLT2i on podocyte function