Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis

Background. To elucidate the molecular mechanism of diabetic nephropathy, a high-density DNA filter array was employed to survey the gene expression p rofile of streptozotocin-induced diabetic CD-1 (ICR) mouse kidneys. Methods. Ten-week-old CD-1 male mice were divided into four groups: (1) con trol, (2) unilaterally nephrectomized (UX) mice, (3) streptozotocin (STZ)-i nduced diabetic (STZ) mice, and (4) STZ mice with unilateral renal ablation (STZ-UX). Pathological changes were examined at 24 weeks after the inducti on. The gene expression profile was compared between the control and STZ mi ce by a Gene Discovery Array (GDA). Results. The glomeruli in UX mouse kidney showed prominent glomerular hyper trophy, while the accumulation of mesangial matrix was minimal. Both STZ an d STZ + UX mice had significant glomerular hypertrophy and glomeruloscleros is, and the lesions were not enhanced by renal ablation. By comparison betw een control and STZ mice, 16 clones that increased in expression with the i nduction of diabetes and 65 clones that decreased in diabetic kidneys were identified. The 37 known genes were related to glucose and lipid metabolism , ion transport, transcription factors, signaling molecules, and extracellu lar matrix-related molecules. The genes known to be involved in cell differ entiation and organogenesis in various tissues (that is, Unc-18 homolog, PO U domain transcription factor 2, lunatic fringe gene homolog, fibrous sheat h component 1, Sox-17, fibulin 2, and MRJ) were found to be differentially expressed in the early phase of diabetic kidneys. Conclusions. Hyperglycemia is a major determinant of glomerulosclerosis in STZ-induced diabetic CD-1 mice, and the altered gene expression in the earl y phase of diabetic kidney may be critical for the development of diabetic nephropathy.