Mechanism of glomerulosclerosis on the basis of cell cycle reguration and differentiation of glomerular epithelial cells.

基于肾小球上皮细胞细胞周期调节和分化的肾小球硬化机制。

基本信息

批准号：
10670154
负责人：
NAGATA Michio
金额：
$ 2.05万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670154/
关键词：
podocyte parietal epithelial cells glomerulosclerosis cell cycle cell cycle inhibitor nephron IL-4 IL-4 ボーマン嚢上皮細胞 cyclin kinase inhibitor 体硬化器官培養 GFP Podocyte differentiation Cell cycle phenotype

项目摘要

This project was aimed to find the mechanism involving cell cycle reguration of glomerlular epithelial cells (podocytes). During first year of 1998, we found that cell cycle quiescent and podocyte differentiation was closely correlated in human fetal kidneys. Cell cycle stunt is tightly cassociated with up-regulation of cell cycle inhibitors, p27 and p57. Cell cycle promotion of presumptive podocytes was partly determined by cyclin A, B1 and D1. In addition, we found low expression of CKIs in cellular crescents and cellular lesion in focal glomeruloscleorsis in human biopsy materials. These proliferating cells virtually expressed cytokeratin indicating parietal epithelial cell phenotype. Thus PECs compensate podocyte loss is an actual pathology promoting glomerulosclerosis.The second year of 1999, we performed in vitro study. Metanephric organ culture showed up-reguration of p27, but not p57 in concert with podocyte differentiation. Thus p27 plays predominant role for the podocyte differentiation and cell cycle stunt. Next, we looked at the effect of Interleukin-4 in podocyte cell culture. We found IL4 stimulate podocyte cell line to form Dome shape. Thus IL-4 may modify cell attachment system, i.e., focal contact.. Finally we used green fluorescent transgenic mice to determine whether inserted promoter is activated with differentiation. Fetal kidneys and metanephric culture system demonstrated podocyte glowing in capillary loop stage. The stimulant for this hybrid promoter needs further investigation.

该项目的目的是找到涉及肾小球上皮细胞（足细胞）的细胞周期回合的机制。在1998年的第一年，我们发现细胞周期的静止和足细胞分化与人胎儿肾脏密切相关。细胞周期特技与细胞周期抑制剂p27和p57的上调紧密相关。推定足细胞的细胞循环促进部分由细胞周期蛋白A，B1和D1确定。此外，我们发现在人体活检材料中，CKI在细胞新月形和局灶性肾小球脊髓病变中的CKI表达较低。这些增殖细胞实际上表达了细胞角蛋白，表明顶叶上皮细胞表型。因此，PEC补偿足细胞损失是一种促进肾小球硬化的实际病理。1999年的第二年，我们在体外研究进行了研究。肾上腺器官培养物显示出p27的升高，但与足细胞分化的一致p57表示。因此，p27在足细胞分化和细胞周期特技表中起主要作用。接下来，我们研究了白介素4对足细胞培养的影响。我们发现IL4刺激足细胞系以形成圆顶形状。因此，IL-4可以修改细胞附着系统，即焦点接触。最后，我们使用了绿色荧光转基因小鼠来确定是否通过分化激活了插入的启动子。胎儿肾脏和跨媒体培养系统在毛细管环阶段表现出足细胞的发光。该混合动力启动子的兴奋剂需要进一步研究。