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学过程中衍生细胞的足细胞，我们产生肾蛋白-CRE/ROSA26小鼠，然后与P21缺乏小鼠交叉并诱导抗辉煌抗体肾小球肾小球肾炎。肾脏显示出明显的蛋白尿与肾小球上皮增生。为了分析这些细胞的起源和表型，分析了几种足细胞标记的免疫组织化学和BRDU的掺入。高细胞病变实际上是LACZ和WT1阴性。此外，我们没有发现lacz+/wt1细胞或lacz+/Synaptopodin-cells。因此，在这种实验性肾上腺肾炎的情况下，并未发生足细胞的去分化。我们现在正在研究侧重于Nestin中间型细丝的功能的足细胞的可塑性，神经源祖细胞，我们发现NISTIN在分化的Podocytes和Cytopysir的分布中，主要表达了NESTIR的分布。永生的足细胞细胞系揭示了过程形成的抑制，暗示了巢穴可塑性的巢穴功能。