Grant: Operating Grant

Background: It is considered that much of the damage to the filtering ability of the kidney in diabetes occurs as a result of a phenomenon known as oxidative stress. Objective: This project hopes to identify new targets in order to develop novel treatments to better treat and prevent diabetic kidney disease. Project description: This proposal postulates that a certain very recently identified form of an enzyme called Nox which promotes oxidative stress known as Nox5, which appear to be preferentially upregulated in the kidney in diabetes, would be an ideal target for generating drugs to reduce the impact of diabetic kidney disease. We will develop a set of mice that possess an abundant level of this stress inducing enzyme in the kidney and test whether their diabetic kidney disease and filtering ability worsens. Kidney disorders remain major causes of morbidity and premature mortality in diabetic individuals. Although currently available treatment strategies addressing, in particular, optimization of glycemic and blood pressure control have been shown to reduce progression of diabetic kidney disease, the effects remain modest. The studies will employ human kidney cells that will be exposed to high glucose concentrations (to mimic the "diabetic milieu") in order to investigate factors which activate the Nox5 enzyme, thereby promoting oxidative stress. These studies will thereby strengthen the rationale to consider Nox5 as a potential new target to develop better treatments to reduce a major burden of diabetes - diabetic kidney disease.