Wada J, Zhang H, Tsuchiyama Y, Hiragushi K, Hida K, Shikata K, Kanwar Y S, Makino H
Department of Medicine III, Okayama University Medical School, Okayama, Japan.
Kidney Int. 2001 Apr;59(4):1363-73. doi: 10.1046/j.1523-1755.2001.0590041363.x.
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.
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).
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.
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.
为阐明糖尿病肾病的分子机制，采用高密度DNA滤膜阵列检测链脲佐菌素诱导的糖尿病CD-1（ICR）小鼠肾脏的基因表达谱。
将10周龄的CD-1雄性小鼠分为四组：（1）对照组，（2）单侧肾切除（UX）小鼠，（3）链脲佐菌素（STZ）诱导的糖尿病（STZ）小鼠，（4）单侧肾切除的STZ小鼠（STZ-UX）。诱导后24周检查病理变化。通过基因发现阵列（GDA）比较对照组和STZ小鼠的基因表达谱。
UX小鼠肾脏的肾小球显示出明显的肾小球肥大，而系膜基质的积聚最少。STZ和STZ+UX小鼠均有明显的肾小球肥大和肾小球硬化，肾切除并未加重病变。通过比较对照组和STZ小鼠，鉴定出16个随糖尿病诱导表达增加的克隆和65个在糖尿病肾脏中表达降低的克隆。37个已知基因与葡萄糖和脂质代谢、离子转运、转录因子、信号分子以及细胞外基质相关分子有关。发现已知参与各种组织细胞分化和器官发生的基因（即Unc-18同源物、POU结构域转录因子2、类lunatic fringe基因同源物、纤维鞘成分1、Sox-17、纤连蛋白2和MRJ）在糖尿病肾脏早期差异表达。
高血糖是链脲佐菌素诱导的糖尿病CD-1小鼠肾小球硬化的主要决定因素，糖尿病肾脏早期基因表达的改变可能对糖尿病肾病的发展至关重要。
