The emerging insight into E3 ligases as the potential therapeutic target for diabetic kidney disease

Diabetic kidney disease (DKD) is a major diabetic complication and global health concern, occurring in nearly 30 % to 40 % of people with diabetes. Importantly, several therapeutic strategies are being used against DKD; however, available treatments are not uniformly effective and the continuous rise in the prevalence of DKD demands more potential therapeutic approaches or targets. Epigenetic modifiers are regarded for their potential therapeutic effects against DKD. E3 ligases are such epigenetic modifier that regulates the target gene expression by attaching ubiquitin to the histone protein. In recent years, the E3 ligases came up as a potential therapeutic target as it selectively attaches ubiquitin to the substrate proteins in the ubiquitination cascade and modulates cellular homeostasis. The E3 ligases are also actively involved in DKD by regulating the expression of several proteins involved in the proinflammatory and profibrotic pathways. Burgeoning reports suggest that several E3 ligases such as TRIM18 (tripartite motif 18), Smurf1 (Smad ubiquitination regulatory factor 1), and NEDD4-2 (neural precursor cell-expressed developmentally downregulated gene 4-2) are involved in kidney epithelial-mesenchymal transition, inflammation, and fibrosis by regulating respective signaling pathways. However, the various signaling pathways that are regulated by different E3 ligases in the progression of DKD are poorly understood. In this review, we have discussed E3 ligases as potential therapeutic target for DKD. Moreover, different signaling pathways regulated by E3 ligases in the progression of DKD have also been discussed.