Grant: Project Grant

Internal organs are covered and protected by specialized cells called epithelia that create and maintain a barrier and allow only highly regulated exchange of materials through the layer. This is vital for normal organ function. These cells can react to injury and have the capacity to repair injured layer. However, sustained injury activate and alter these cells, processes that can lead to dysregulated healing. This process can ultimately destroy organs, including the kidney. Kidney disease is a huge problem, as increasing number of people suffer from diabetes and high blood pressure, that cause kidney disease. The overall aim of this proposal is to find new ways to prevent kidney diseases by defining ways through which epithelial contribute to dysregulated healing. Our work pointed to the role of a specialized molecule localized at the connection between epithelia in the kidney, called claudin-2. This protein regulates cell growth and harmful chemicals causes a drop in its levels. Thus, in this proposal we suggest that claudin-2 controls how epithelial layers regenerate following injury. During kidney disease claudin-2 is lost, which causes abnormal regeneration, that eventually can lead to altered healing and kidney scarring, a fatal condition. Using biochemical and cell biological methods, we will test these new roles of claudin-2 and determine how it functions. We will use animal models of organ injury to further explore what happens to claudin-2 during injury. Our studies will uncover new mechanisms underlying kidney diseases and help find novel targets for designing drugs to treat kidney failure.