Projects and Grants

Grant Title: THE ROLE OF SIRT1/FOXO4 PATHWAY IN PODOCYTE APOPTOSIS OF DIABETES MELLITUS

Funding Agency: NIH/NIDDK

Diabetic kidney disease is the number one cause of renal failure requiring dialysis or renal transplantation in the US. Podocyte loss contributes to the development and progression of diabetic kidney disease. Patients with diabetes mellitus have high serum levels of advanced glycation endproducts (AGEs), which can trigger podocyte apoptosis by activating a Foxo transcription factor. Our preliminary results suggest that AGEs activate Foxo by increasing its acetylation. Sirtuin is a protein deacetylase that targets Foxo for de-acetylation. We found that Sirt1 expression is suppressed in the diabetic condition. We hypothesize that suppression of Sirt1 in the diabetic condition enhances acetylation and activation of Foxo, which contributes to the apoptosis of podocytes.