The prevalence of obesity has increased significantly over the last few decades. This increase in obesity is associated with an increase in its complications including insulin resistance, cardiovascular diseases, and glomerular diseases. Podocyte injury during glomerular diseases is often characterized by alterations in the cytoskeleton and effacement of foot processes leading to proteinuria. Pyruvate kinase M2 regulates the final step of glycolysis and catalyzes the dephosphorylation of phosphoenolpyruvate (PEP) to pyruvate and the production of ATP. Our preliminary data shows increased PKM2 expression and alteration in PKM2 catalytic activity in podocytes in lipopolysaccharide (LPS)-induced renal injury model. Therefore, the goal of this study was to investigate the contribution of PKM2 to acute renal injury and decipher the molecular mechanisms.
We generated mice with specific deletion of PKM2 in podocyte, and we assessed the alterations in kidneys function after LPS injection.
Here, we report an increase in PKM2 expression and phosphorylation in response to LPS in control mice. Interestingly, the deletion of PKM2 in podocyte was associated with alterations in urinary proteins, blood urea nitrogen, and kidney to body weight ratio. In addition, mice with PKM2 deletion in podocytes exhibited significant differences in renal mRNA levels and serum concentrations of inflammatory cytokines compared to controls. The effects of PKM2 deletion on LPS-induced podocytes injury were mediated, at least partially, through alterations in major signaling pathways involved in podocytes homeostasis.
These findings identify a novel role for PKM2 in podocytes and warrant additional investigation into the role of PKM2 in podocytes function.