Grant: Master's Award: Canada Graduate Scholarships

The kidneys play a central role in maintaining blood pressure by filtering plasma waste. The active units of the kidneys known as the nephrons contain the filtration apparatus known as the glomerulus. The final barrier to important plasma proteins in glomerular filtration is composed of highly specialized cells known as podocytes with interdigitating projections that form a barrier to important plasma proteins. Perturbation of these cells leads to compromised kidney function, clinically characterized by the presence of protein in the urine. In many chronic kidney diseases, there is an overproduction of hormones known as prostaglandins. Our lab has hypothesized that high levels of these hormones predispose podocytes to injury. Important proteins known as Rho, Rac and Cdc42 regulate cellular reorganization in their own capacity. Since the proper function of the podocyte is based on their complexe cellular architecture, we will examine the impact of increased prostaglandin production on Rho, Rac and Cdc42 activity in a diabetic setting on podocyte and kidney health. For this study, mice with prostaglandin receptor gene deletions will be generated and type I diabetes will be induced. The progression of diabetic nephropathy in the mice will be evaluated by proteinuria, glomerular and podocyte damage. Since diabetic nephropathy is one of the leading causes of end stage renal failure, we propose to study how the elevation of prostaglandins in a diabetic setting can cause podocyte and glomerular loss of function leading to proteinuria and kidney failure in mice. The mechanisms leading to proteinuria are incompletely understood and the need for elucidating new molecular targets and developing efficient therapies is greater than ever. The results and observations from this study could be an important contribution to the present literature on diabetic kidney disease.