Grant: Project Grant

Diabetes is the most common cause of kidney failure, leading to scarring of the filtering units of the kidneys. Patients with diabetes have high glucose levels in their blood. High glucose causes kidney cells called mesangial cells to make scar proteins. These scar proteins accumulate in the filtering units of the kidneys and prevent them from functioning properly. It is not yet known how high glucose levels cause kidney cells to produce these scar proteins. Our previous studies showed that absence of the protein caveolin-1 from kidney cells and from kidneys protected against scarring due to diabetes. Since caveolin-1 is difficult to change with treatment, we looked to see the differences in micro RNA levels between kidney cells with and without caveolin-1. Here we found micro RNA 299a-5p levels to be decreased in kidney cells without caveolin-1. In diabetic kidneys and kidney cells exposed to high glucose, micro RNA 299a-5p is increased, and blocking it prevents cells from making scar proteins. In our studies, we would like to understand how micro RNA-299a-5p allows high glucose to direct kidney cells to make scar proteins, and whether blocking the function of miRNA-299a-5p will prevent kidney scarring and help to prevent kidney function from getting worse in mice with diabetes. Drugs which block other molecules like micro RNA-299a-5p have already been successfully used in patients. If our studies show that blocking micro RNA-299a-5p prevents or improves diabetic kidney disease, this will give us a new treatment to test in patients with kidney disease due to diabetes.