Independent investigation into pathophysiology of diabetes support that the stress response protein REDD1 (Regulated in Development and DNA Damage 1) contributes to the development of diabetic complications. We have observed that REDD1 expression specifically in podocyte facilitates renal injury, as evidenced by increased urine albumin excretion, glomerular hypertrophy, and mesangial matrix deposition. Notably we observed that podocyte-specific deletion of REDD1 preserved glomerular architecture and subsequent loss of renal function.   

More specifically, we identified that under hyperglycemic conditions, REDD1 promoted NF-κB-dependent transcription of the calcium ion channel TRPC6 in podocytes resulting in increased intracellular calcium entry, and cytoskeletal remodeling. Our findings provide evidence to support a model wherein enhanced REDD1 expression in podocytes leads to their failure to properly adapt to the diabetic metabolic environment, resulting in podocytopenia and microalbuminuria. These data support the possibility that therapeutics targeting REDD1 in podocytes could be beneficial for DN.