Role of KAP expression in the diabetic kidney

Ohio University Athens, Athens OH

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Abstract

DESCRIPTION (provided by applicant): Kidney damage is a frequent complication of both type I and type II diabetes, often ending in kidney failure, or end-stage renal disease (ESRD). Diabetic nephropathy, the single most common cause of ESRD, is a progressive disease that takes several years to develop and often goes undiagnosed. The long-term goal of this project is to design specific, targeted markers and therapeutic approaches for the diagnosis, treatment, and prevention of human diabetic kidney disease. Toward this end, previous work identified a cDNA whose mRNA expression decreases markedly with increasing kidney damage, both in a diabetes-dependent and in a diabetes-independent mouse model of glomeruloscierosis. This cDNA encodes kidney androgen-regulated protein (KAP), a kidney-specific protein found only in renal proximal tubule cells. Since decreasing levels of KAP mRNA are associated with progressive kidney damage, it is proposed that maintenance of high levels of KAP mRNA expression will protect the kidney from glomerular hypertrophy and diabetic damage. This hypothesis will be tested by expressing KAP mRNA in the kidneys of mice under the direction of a heterologous promoter and then assessing the extent of kidney damage after induction of diabetes by streptozotocin injection. Acceptance of the hypothesis could lead to the development of KAP as a therapeutic drug for the prevention of kidney damage.