|Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis|
|Wada, J; Zhang, H; Tsuchiyama, Y; Hiragushi, K; Hida, K; Shikata, K; Kanwar, YS; Makino, H|
|关键词||CD-1 (ICR) mouse diabetic nephropathy hyperglycemia tubulointerstitial fibrosis end-stage renal failure|
|WOS标题词||Science & Technology|
|类目[WOS]||Urology & Nephrology|
|研究领域[WOS]||Urology & Nephrology|
|关键词[WOS]||ACTIVATED PROTEIN-KINASE ; DNA HELICASE-II ; GLUCOSE-METABOLISM ; EXTRACELLULAR-MATRIX ; RENAL HYPERTROPHY ; EPITHELIAL-CELLS ; BINDING-PROTEIN ; MESSENGER-RNA ; MOUSE KIDNEY ; MELLITUS|
Background. To elucidate the molecular mechanism of diabetic nephropathy, a high-density DNA filter array was employed to survey the gene expression profile of streptozotocin-induced diabetic CD-1 (ICR) mouse kidneys.
Methods. Ten-week-old CD-1 male mice were divided into four groups: (1) control, (2) unilaterally nephrectomized (UX) mice, (3) streptozotocin (STZ)-induced diabetic (STZ) mice, and (4) STZ mice with unilateral renal ablation (STZ-UX). Pathological changes were examined at 24 weeks after the induction. The gene expression profile was compared between the control and STZ mice by a Gene Discovery Array (GDA).
Results. The glomeruli in UX mouse kidney showed prominent glomerular hypertrophy, while the accumulation of mesangial matrix was minimal. Both STZ and STZ + UX mice had significant glomerular hypertrophy and glomerulosclerosis, and the lesions were not enhanced by renal ablation. By comparison between control and STZ mice, 16 clones that increased in expression with the induction 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 extracellular matrix-related molecules. The genes known to be involved in cell differentiation and organogenesis in various tissues (that is, Unc-18 homolog, POU domain transcription factor 2, lunatic fringe gene homolog, fibrous sheath 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 early phase of diabetic kidney may be critical for the development of diabetic nephropathy.
|作者单位||1.Okayama Univ, Sch Med, Dept Med 3, Okayama 7008558, Japan|
2.Beijing Med Univ, Teaching Hosp 1, Dept Nephrol, Beijing 100083, Peoples R China
3.Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA
|Wada, J,Zhang, H,Tsuchiyama, Y,et al. Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis[J]. KIDNEY INTERNATIONAL,2001,59(4):1363-1373.|
|APA||Wada, J.,Zhang, H.,Tsuchiyama, Y.,Hiragushi, K.,Hida, K.,...&Makino, H.(2001).Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis.KIDNEY INTERNATIONAL,59(4),1363-1373.|
|MLA||Wada, J,et al."Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis".KIDNEY INTERNATIONAL 59.4(2001):1363-1373.|