Identification of Cross-Species Shared Transcriptional Networks of Diabetic Nephropathy in Human and

Murine models are valuable instruments in defining the pathogen-esis of diabetic nephropathy (DN), but they only partially re-capitulate disease manifestations of human DN, limiting their utility. To define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expres-sion was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2, C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared human–mouse cross-species glo-merular transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db), and 162 (Human-BKS eNOS2/2 db/db) gene nodes were generated. Shared nodes across all net-works reflected established pathogenic mechanisms of diabete