PLK2 Plays an Essential Role in High D-Glucose-Induced Apoptosis, ROS Generation and Inflammation in Podocytes

Abstract

Diabetic kidney disease (DKD) is a serious complication of hyperglycemia. Currently, there is no effective therapeutic intervention for DKD. In this study, we sought to provide a set of gene profile in diabetic kidneys. We identified 338 genes altered in diabetes-induced DKD glomeruli, and PLK2 exhibited the most dramatic change. Gene set enrichment analysis (GSEA) indicated multiple signaling pathways are involved DKD pathogenesis. Here, we investigated whether PLK2 contributes to podocyte dysfunction, a characteristic change in the development of DKD. High D-glucose (HDG) significantly increased PLK2 expression in mouse podocytes. Suppressing PLK2 attenuated HDG-induced apoptosis and inflammatory responses both in vitro and in vivo. NAC, an antioxidant reagent, rescued HDG and PLK2 overexpression-induced kidney injuries. In summary, we demonstrated that silencing PLK2 attenuates HDG-induced podocyte apoptosis and inflammation, which may serve as a future therapeutic target in DKD.

Thymol alleviates AGEs-induced podocyte injury by a pleiotropic effect via NF-κB-mediated by RhoA/ROCK signalling pathway

“…The inflammation seen in DN does not merely activate macrophages and neutrophil infiltration; it also affects the podocytes themselves, which are the main source of inflammatory cytokines in response to stimuli [32]. We found that AGE can promote the expression of IL-6 and TNF-α in podocytes by activating the NF-kB pathway.…”

ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes

“…Previous studies have shown that modifications of the electron transport chain which render the system less efficient contributes to increased ROS production (43)(44)(45). Indeed, both clinical and experimental DKD are characterized by elevated ROS (45)(46)(47)(48)(49). For example, glomeruli isolated from db/db mice have increased ROS production when compared with db/+ mice (50).…”

Proteome Analysis in a Mammalian Cell Line Reveals that PLK2 Is Involved in Avian Metapneumovirus Type C (aMPV/C)-Induced Apoptosis

“…PLK2 has been reported to exert an antioxidant function and prevent p53-and ROS-coordinated cell death [39]. However, the opposite effect of PLK2 on p53 and ROS generation has also been observed in high D-glucose-induced apoptosis [41]. To investigate whether PLK2-regulated apoptosis is associated with mitochondrial dysfunction, we next measured ROS in cells after aMPV infection.…”

“…glucose-induced apoptosis [41]. To investigate whether PLK2-regulated apoptosis is associated with mitochondrial dysfunction, we next measured ROS in cells after aMPV infection.…”