Grant: Operating Grant

Diabetes is the most common cause of kidney failure. In the diabetic kidney, scar proteins (matrix) accumulate in the filtering units (glomeruli) and prevent them from functioning properly. It is not yet known how high glucose levels cause glomerulus (mesangial) cells to produce matrix. Our recent studies have shown that in mesangial cells exposed to high glucose, the protein ADAM17 is activated and involved in matrix production by causing the activation of the epidermal growth factor receptor (EGFR). We have previously shown that EGFR activation by high glucose leads mesangial cells to produce matrix proteins. I plan to investigate exactly how ADAM17 is activated by high glucose, and whether blocking its activation with drugs can slow or prevent the development of kidney disease in a rat model of diabetes. If effective, this would be a potential new treatment for people whose diabetes has affected their kidneys.