Silencing of PFKFB3 protects podocytes against high glucose-induced injury by inducing autophagy

Diabetic nephropathy (DN) is a diabetic complication that threatens the health of patients with diabetes. In addition, podocyte injury can lead to the occurrence of DN. The protein 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) may be associated with diabetes; however, the effects of PFKFB3 knockdown by small interfering (si)RNA on the growth of podocytes remains unknown. To investigate the mechanism by which PFKFB3 mediates podocyte injury, MPC5 mouse podocyte cells were treated with high-glucose (HG), and cell viability and apoptosis were examined by Cell Counting Kit-8 assay and flow cytometry, respectively. In addition, the expression of autophagy-related proteins were measured using western blot analysis and immunofluorescence staining. Cell migration was investigated using a Transwell assay and phalloidin staining was performed to observe the cytoskeleton. The results revealed that silencing of PFKFB3 significantly promoted MPC5 cell viability and inhibited apoptosis. In addition, the migration of the MPC5 cells was notably downregulated by siPFKFB3. Moreover, PFKFB3 silencing notably reversed the HG-induced decrease in oxygen consumption rate, and the HG-induced increase in extracellular acidification rate was rescued by PFKFB3 siRNA. Furthermore, silencing of PFKFB3 induced autophagy in HG-treated podocytes through inactivating phosphorylated (p-)mTOR, p-AMPKα, LC3 and sirtuin 1, and activating p62. In conclusion, silencing of PFKFB3 may protect podocytes from HG-induced injury by inducing autophagy. Therefore, PFKFB3 may serve as a potential target for treatment of DN.