Grant: Operating Grant

Diabetes is a very common cause of kidney failure, leading to scarring of the filtering units of the kidneys. High glucose causes kidney cells called mesangial cells to make a protein called transforming growth factor beta (TGFbeta) which induces cells to make scar proteins. We have previously shown that a protein called caveolin-1 is needed for mesangial cells to make TGFbeta and scar proteins. We also showed that mice which do not have caveolin-1 are protected from developing diabetic kidney disease. Inhibiting caveolin-1 in patients, however, is difficult. In trying to establish exactly how caveolin-1 protects against diabetic kidney disease, we found that mesangial cells and kidneys without caveolin-1 have high levels of a protein called follistatin. This protein blocks the actions of TGFbeta and another protein (activin A) which both direct cells to make scar proteins. Follistatin levels are decreased in diabetic kidneys and by treating mesangial cells with high glucose. In this project we will investigate how caveolin-1 regulates the production of follistatin, and whether treating mice with diabetes with follistatin can inhibit or delay the development of kidney disease.