Functional genomics of diabetic nephropathy in a newly‐characterized rat model

Abstract

Diabetic nephropathy (DN) is the most common cause of end stage renal disease in the United States and approximately 40% of all diabetics eventually develop the disorder. A meta‐analysis of publicly available microarray data was performed to find genes that were consistently misexpressed in DN. From this list, those genes that also segregate with a predisposition for DN in humans were identified. Thus, a list of genes that are misexpressed both in patients and mouse models of DN, as well as linked to DN susceptibility, was prepared. This list of candidate genes, likely important for the onset and progression of DN, included vascular endothelial growth factor (VEGF), protein kinase B (Akt/Pkb), phospholipase Cγ (PLCγ), and interestingly PLCε, which is mutated in a familial form of nephrotic syndrome. These analyses, together with our recent observation of increased urinary VEGF in very early DN, suggest a central role for the VEGF pathway in DN onset and progression. The role of these genes is currently being investigated in ZSF rats, a newly‐characterized rat model for DN (Prabhakar et al., JASN, 2007). The identification of genes involved in DN pathogenesis could lead to better diagnostics and therapies for DN.Supported by the Larry and Jane Woirhaye Foundation for renal research.