Chronic hyperglycemia contributes to development of diabetic kidney disease by promoting glomerular injury. Our observations indicate that hyperglycemic conditions promote expression of the stress response protein regulated in development and DNA damage response 1 (REDD1) in the kidney in a manner that contributes to the development of oxidative stress and renal injury. 

The transcription factor Nrf2 regulates expression of over 200 antioxidant response genes by binding to an ARE enhancer region of their promoters.  Using in vitro molecular techniques we have determined that expression of the stress response protein REDD1 is required for aberrant Nrf2 activity within podocytes that results in enhanced production of reactive oxygen species. The net prooxidant environment within these cells contributes to altered pathology that compromises filtration function in the kidney.