Project 172117

In diabetes, kidney disease can result when highly specialized cells, known as podocytes become injured. Once damaged, these podocytes can no longer help filter the blood since they allow proteins into urine, a condition known as proteinuria. This condition can be improved by nonsteroidal anti-inflammatory drugs (NSAIDs) such as Aspirin, Motrin, and ibuprofen. These drugs block the production of hormones known as prostanoids. These prostanoids carry out their roles by stimulating a series of receptors located throughout the kidney - including the podocytes. Unfortunately NSAIDs are rarely used in the clinic since they can bring about adverse side effects on the kidney by reducing blood flow. Thus prostanoids apparently contribute to 'protective' and 'damaging' processes in the kidney. We wish to identify the target of these drugs which mediates proteinuria in type I diabetes, so that newer - more specific drugs could be designed to avoid the 'protective' receptors while targeting those which 'damage' the filters of the kidney. Our research program generates mice with altered levels of these prostanoid hormone receptors and subjects them to models of human kidney disease. We can then ascertain whether proteinuria is blocked or worsened. Demonstration of critical role for specific prostanoid receptors in diabetic kidney disease may identify therapeutic targets for new drugs.