Project Summary Autosomal Dominant Polycystic kidney disease (ADPKD) is characterized by numerous cysts within the kidneys of afflicted individuals. The cysts formed in ADPKD can greatly enlarge the kidneys while replacing the normal kidney structures, resulting in reduced kidney function and progression to end-stage renal disease, that can only be treated by lifelong dialysis or kidney transplants. As a disease that affects 1 in 800~1000 individuals, ADPKD is among the most common genetic disorders. In the United States, there are 600,000 individuals, and worldwide 12.5 million, with PKD [1]. Thus, ADPKD represents a major public health issue, and accounts for hundreds of millions (and perhaps over a billion) of dollars in health care costs, particularly for dialysis treatments and the cost of drugs that prevent transplant rejections, as well as the cost involved of decreased productivity and impaired quality of life of individuals with ADPKD. For all these reasons, it is of great importance to discover treatments that directly affect the molecular causes of ADPKD, and that will prevent the progression to end- stage renal disease and dialysis or transplantation. Over the past 5 years the Kreidberg laboratory has investigated the role of Wnt signaling in the pathogenesis of ADPKD. Dr. Kreidberg’s laboratory has found that Wnt signaling and β- catenin expression is highly elevated in cyst lining cells in ADPKD. In this grant they propose to extend their studies to understand how a putative β-catenin target gene, fibronectin, affects cyst formation. Fibronectin is a key extracellular matrix gene primarily found in a mesenchymal matrix, but over-expressed in cystic kidneys. We will study the role of integrin:fibronectin interactions in ADPKD.