From bench to bedside: lessons learned from translational podocyte research

Polat et al. report that mice with a podocyte-specific expression of a constitutively active Rac1 form displayed similar injury and albuminuria, regardless of transient receptor potential canonical 5 activity. This article confirms the pathogenic role of deregulated Rac1 and challenges models involving the role of transient receptor potential canonical 5 in podocytes. We learned from this study and propose a roadmap for this controversial field to help new drug candidates succeed in clinical trials and safely reach patients. Polat et al. report that mice with a podocyte-specific expression of a constitutively active Rac1 form displayed similar injury and albuminuria, regardless of transient receptor potential canonical 5 activity. This article confirms the pathogenic role of deregulated Rac1 and challenges models involving the role of transient receptor potential canonical 5 in podocytes. We learned from this study and propose a roadmap for this controversial field to help new drug candidates succeed in clinical trials and safely reach patients. The small GTPase regulatory protein Rac1 drives podocyte injury independent of cationic channel protein TRPC5Kidney InternationalVol. 103Issue 6PreviewTransient receptor potential canonical channels (TRPCs) are non-selective cationic channels that play a role in signal transduction, especially in G -protein-mediated signaling cascades. TRPC5 is expressed predominantly in the brain but also in the kidney. However, its role in kidney physiology and pathophysiology is controversial. Some studies have suggested that TRPC5 drives podocyte injury and proteinuria, particularly after small GTPase Rac1 activation to induce the trafficking of TRPC5 to the plasma membrane. Full-Text PDF