Expression and significance of the P2X7 purinoceptor in Diabetic Nephropathy

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Diabetic kidney disease (diabetic nephropathy) is a serious and increasingly prevalent complication of diabetes; it is characterised by progressive scarring of the kidney glomeruli (the filtration units). Despite improvements in the treatment of diabetes, renal function in many patients continues to decline, eventually requiring dialysis or transplantation. Current treatments slow progression in a proportion of patients but do not prevent this, and there is a pressing need for new forms of treatment. An ATP receptor known as the P2X7 receptor (P2X7R) that can be expressed on the surface of cells in the kidney has been linked to kidney injury, including in diabetes. The aim of this proposal is to investigate whether this receptor is involved in diabetic nephropathy. The studies outlined involve a combined approach using human kidney biopsy sections and urine samples, and a model of diabetes in mice that do not express P2X7R (if P2X7R is important in diabetes, lack of this receptor should reduce disease severity), as well as in vitro kidney cell cultures, to define the mechanisms whereby P2X7R may cause disease. Demonstrating a role for P2X7R in diabetic nephropathy could lead to development of a novel therapy for this intractable disease.