Regeneration of sclerosed glomeruli : Mechanism of dedifferentiation and phenotypic changes in podocytes and induce redifferentiation.

硬化肾小球的再生：足细胞去分化和表型变化并诱导再分化的机制。

• 批准号: 17590818
• 负责人: NAGATA Michio
• 金额: $ 2.18万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590818/
• 关键词: kidney; glomerulosclerosis; podocyte; differentiation; phenotype; glomerulonephritis; nestin; regeneration; トランスジェニックマウス; ROSAマウス; nephrin-Cre; 抗基底膜抗体腎炎; 上皮脱分化

To monitor podocytes derived cells in the pathologic process of glomerular disease, we generate Nephrin-Cre/Rosa26 mice and then we crossed them with p21 deficient mice and induced anti-glomerular antibody glomerulonephritis. The kidney showed marked proteinuria coupled with glomerular epithelial hyperplasia. To analyze the origin and phenotype of these cells, immunohistochemistry for several podocytes markers and incorporation of BrdU was analyzed. Hypercellular lesions were virtually both LacZ and WT1 negative. In addition, we did not find out for LacZ+/WT1-cells or LacZ+/synaptopodin-cells. Thus podocytes dedifferentiation is not occurring in this setting of experimental glomerulonephritis.We are now investigating the plasticity of podocytes focusing on the function of nestin intermediate filament, neurogenic progenitor marker, we found nestin is predominantly expressed in the differentiated podocytes and cytoplasmic distribution of nestin is different from that of actin.siRNA of nestin for immortalized podocytes cell line reveals suppression of process formation suggesting nestin function for podocytes plasticity.

为了监测肾小球疾病病理过程中足细胞衍生的细胞，我们产生Nephrin-Cre/Rosa 26小鼠，然后将它们与p21缺陷小鼠杂交，并诱导抗肾小球抗体肾小球肾炎。肾脏显示明显的蛋白尿伴肾小球上皮增生。为了分析这些细胞的起源和表型，分析了几种足细胞标志物的免疫组织化学和BrdU的掺入。高细胞病变几乎都LacZ和WT 1阴性。此外，我们没有发现LacZ+/WT 1-细胞或LacZ+/synaptopodin-细胞。因此，足细胞去分化在实验性肾小球肾炎中没有发生。我们现在正在研究足细胞的可塑性，重点是巢蛋白中间丝，神经源性祖细胞标志物，我们发现巢蛋白主要在分化的足细胞中表达，并且巢蛋白的胞浆分布与肌动蛋白不同。巢蛋白对永生化足细胞系的siRNA显示突起形成受到抑制提示巢蛋白对足细胞可塑性的作用。