Uninephrectomy of diabetic OVE26 mice greatly accelerates albuminuria, fibrosis, inflammatory cell infiltration and changes in gene expression.
Uninephrectomy of diabetic OVE26 mice greatly accelerates albuminuria, fibrosis, inflammatory cell infiltration and changes in gene expression.
复制标题
DOI：
10.1159/000327586
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Epstein PN
中科院分区：
文献类型：
--
作者：
Zheng S;Huang Y;Yang L;Chen T;Xu J;Epstein PN
OVE26 （OVE）小鼠提供了一种有价值的晚期糖尿病肾病（DN）模型，但它们需要8个月的时间才能发展为中度间质纤维化和肾小球滤过率（GFR）降低。该项目的目的是产生一个更快速和先进的DN模型。在2月龄时对OVE和FVB小鼠进行单肾切除术。蛋白尿、GFR、肾小球硬化、间质纤维化、基因表达和单核细胞浸润被评估为糖尿病和未肾切除术的功能。未切除肾的小鼠蛋白尿、单核细胞浸润、肾系膜基质扩张和肾纤维化明显加快。8月龄时，未切除肾后10周的DN比未治疗的OVE小鼠更严重。在非糖尿病小鼠中，肾切除对这些特征几乎没有影响。微阵列研究表明，肾切除OVE小鼠的纤维化和细胞浸润加速伴随着纤维化和炎症典型通路中相应的基因表达变化。肾切除术大大加速了糖尿病肾损害的所有特征。该程序提供术后10周的时间来检查DN的病理变化。该模型对于测试新疗法和分析DN中蛋白尿和纤维化的进展可能特别有用。
OVE26 (OVE) mice provide a valuable model of advanced diabetic nephropathy (DN), but they take 8 months to develop moderate interstitial fibrosis and reduced glomerular filtration rate (GFR). The aim of this project was to produce a more rapid and advanced model of DN. Uninephrectomy was applied to OVE and FVB mice at 2 months of age. Albuminuria, GFR, glomerulosclerosis, interstitial fibrosis, gene expression and monocyte infiltration were evaluated as a function of diabetes and uninephrectomy. Albuminuria, monocyte infiltration, mesangial matrix expansion and renal fibrosis were greatly accelerated in uninephrectomized mice. DN was more advanced 10 weeks after uninephrectomy than in untreated OVE mice at 8 months of age. Uninephrectomy had almost no effect on these characteristics in non-diabetic mice. Microarray studies indicated that the accelerated fibrosis and cell infiltration in nephrectomized OVE mice were accompanied by corresponding gene expression changes in canonical pathways for fibrosis and inflammation. Uninephrectomy greatly accelerates all features of diabetic renal damage. This procedure provides a 10-week period after surgery to examine very large changes in the pathology of DN. The model may be particularly useful for testing new therapies and for analysis of the progression of albuminuria and fibrosis in DN.
登录
查看更多内容
DOI：
10.1073/pnas.120055097
发表时间：
2000-07-05
影响因子：
11.1
作者：
Ziyadeh, FN;Hoffman, BB;Sharma, K
通讯作者：
Sharma, K
影响因子：
19.6
作者：
Dunn, SR;Qi, ZH;Sharma, K
通讯作者：
Sharma, K
影响因子：
19.6
作者：
Chow, F;Ozols, E;Tesch, GH
通讯作者：
Tesch, GH
影响因子：
3.5
作者：
Hartner, A;Eifert, T;Amann, K
通讯作者：
Amann, K
影响因子：
--
作者：
Powell, David W.;Bertram, Clinton C.;Klein, Jon B.
通讯作者：
Klein, Jon B.