A novel mouse model of podocyte depletion.
A novel mouse model of podocyte depletion.
复制标题
DOI：
10.1159/000342369
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Spurney RF
中科院分区：
文献类型：
--
作者：
Wang L;Tang Y;Howell DN;Ruiz P;Spurney RF
这些研究的目的是检查足细胞耗尽损伤后肾小球修复的能力。我们建立了转基因（TG）小鼠表达酵母酶胞嘧啶脱氨酶，特别是在肾小球足细胞。在这些TG动物中，前药5-氟胞嘧啶（5-FC）转化为5-氟尿嘧啶（5-FU）并促进细胞死亡。治疗后1-2周，5-FC剂量增加导致蛋白尿分级增加，在10周时间点恢复至对照水平。光学显微镜检查显示在2周时间点的最小病理学，但电子显微镜检查发现足突消失以及肾小球基底膜复制的局灶性区域，免疫组化研究检测到足细胞凋亡和Wilms肿瘤蛋白1（WT 1）阳性细胞数量减少。然而，到10周时间点，WT 1阳性细胞的数量与对照组相似，少数小鼠出现肾小球硬化灶性区域。与5-FC对足细胞数量的影响一致，足细胞nephrin，podocin，synaptopodin和podocalyxin的mRNA表达以类似的时间方式改变。肾小球在足细胞耗竭损伤后具有显著的修复能力。
The goal of these studies was to examine the capacity for glomerular repair after a podocyte depleting injury. We created transgenic (TG) mice expressing the yeast enzyme cytosine deaminase specifically in glomerular podocytes. In these TG animals, the prodrug 5-flucytosine (5-FC) is converted to 5-fluorouracil (5-FU) and promotes cell death. Treatment with increasing dosages of 5-FC caused graded increases in proteinuria 1–2 weeks after treatment, which returned to control levels by the 10-week time point. Light microscopic examination revealed minimal pathology at the 2-week time point, but electron microscopy revealed found foot process effacement as well as focal areas of glomerular basement membrane duplication, and immunohistochemical studies detected podocyte apoptosis and a decrease in the number of Wilms tumor protein 1 (WT1) positive cells. By the 10-week time point, however, the number of WT1 positive cells was similar to controls and a few mice had developed focal areas of glomerulosclerosis. Consistent with the effects of 5-FC on podocyte number, expression of the podocyte mRNAs for nephrin, podocin, synaptopodin and podocalyxin were altered in a similar temporal fashion. The glomerulus has a significant capacity for repair after a podocyte depleting injury.
登录
查看更多内容
影响因子：
6
作者：
Macconi, Daniela;Sangalli, Fabio;Remuzzi, Andrea
通讯作者：
Remuzzi, Andrea
影响因子：
7.7
作者：
Dalla Vestra, M;Masiero, A;Fioretto, P
通讯作者：
Fioretto, P
影响因子：
19.6
作者：
Kim, YH;Goyal, M;Wiggins, R
通讯作者：
Wiggins, R
影响因子：
6.1
作者：
Alcázar, JM;Marín, R;Mora-Macía, J
通讯作者：
Mora-Macía, J
DOI：
10.1083/jcb.139.1.193
发表时间：
1997-10-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mundel P;Heid HW;Mundel TM;Krüger M;Reiser J;Kriz W
通讯作者：
Kriz W