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An impact of HSP genes as new therapeutic target moleculesf or diabetic neplunpathy

HSP 基因作为糖尿病肾病新治疗靶分子的影响

基本信息

批准号：
17590926
负责人：
ARAKI Shin-ichi
金额：
$ 2.37万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590926/
关键词：
Diabetes Diabetic Npehropathy gene

项目摘要

To explore new therapeutic target molecules which involve in the development of diabetic nephropathy, we created a time course data of gene expression profiles in the diabetic kidney by a DNA microarray method. Gene expression of the genes which belonged to Heat Shock Protein (HSP), stress responsiveness chaperonin, was inhibited in the kidney of the type 2 diabetic model mice, db/db mice, in comparison to the control mice, db/m nice, over the time-course. The protein levels of HSP70 were increased in the kidney from db/db mice only at the early course of diabetes and were then decreased. In cultured mesengial cells, high glucose medium induced the HSP70 expression, whereas oxidative stress inhibited the mRNA levels and protein levels of HSP70. In the mesangial cells which were constitutively over-expressed HSP70, oxidative stress-induced apoptosis was prevented. Erythropoietin which has a reno-protective effect was induced HSP70 expression in the renal cells and the kidney. These results suggest that, in the kidney of type 2 diabetic model mice, HSP70 expression first increases in response to hyperglycemia and then decreases due to oxidative stress enhanced by chronic diabetic condition. Thus, the failure of the anti-oxidative stress defense mechanism of HSP70 may involve in the development of diabetic nephropathy and an induction of HSP70 might be a tool to prevent diabetic nephropathy

为了探索参与糖尿病肾病发生发展的新的治疗靶分子，我们利用DNA微阵列技术建立了糖尿病肾脏基因表达谱的时程数据。与对照小鼠db/mnice相比，在2型糖尿病模型小鼠db/db小鼠的肾脏中，属于热休克蛋白（HSP）、应激反应伴侣蛋白的基因表达随时间推移受到抑制。db/db小鼠肾脏中HSP 70蛋白水平仅在糖尿病早期升高，随后下降。在培养的肠系膜细胞中，高糖诱导HSP 70的表达，而氧化应激抑制HSP 70的mRNA水平和蛋白水平。在组成性过表达HSP 70的系膜细胞中，氧化应激诱导的凋亡被阻止。具有肾脏保护作用的促红细胞生成素可诱导肾细胞和肾脏HSP 70表达。这些结果表明，在2型糖尿病模型小鼠的肾脏中，HSP 70表达首先响应于高血糖而增加，然后由于慢性糖尿病状况增强的氧化应激而降低。因此，HSP 70的抗氧化应激防御机制的失效可能参与了糖尿病肾病的发生发展，诱导HSP 70的表达可能是预防糖尿病肾病的一种手段