Cells of Renin Lineage Are Progenitors of Podocytes and Parietal Epithelial Cells in Experimental Glomerular Disease
Cells of Renin Lineage Are Progenitors of Podocytes and Parietal Epithelial Cells in Experimental Glomerular Disease
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DOI：
10.1016/j.ajpath.2013.04.024
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发表时间：
2013-08-01
影响因子：
6
通讯作者：
Shankland, Stuart J.
中科院分区：
文献类型：
--
作者：
Pippin, Jeffrey W.;Sparks, Matthew A.;Shankland, Stuart J.
肾小球损伤导致足细胞丢失，这一过程直接导致肾小球瘢痕形成和肾功能下降。固有的修复过程受到足细胞无法再生的限制。居住在肾小球毛细血管旁的肾素系细胞据报道具有祖细胞能力。我们研究肾素系细胞是否能在足细胞损伤后重新填充肾小球，并作为肾小球上皮细胞的祖细胞。在成年Ren1cCreER x Rs-tdTomato-R、Ren1cCre x Rs-ZsGreen-R和Ren1dCre x Z/EG报告小鼠中表达肾素的肾细胞进行了遗传命运定位。细胞毒性抗足细胞抗体诱导三种细胞特异性报告小鼠足细胞耗竭。足细胞数量减少后，肾小球内肾素谱系标记细胞数量显著增加，沿鲍曼囊、肾小球丛或两者均呈局灶性分布。鲍曼囊内的细胞亚群激活肾小球壁上皮细胞标记物配对盒蛋白PAX2和claudin-1的表达。肾小球簇内的一部分标记细胞表达足细胞标记物Wilms肿瘤蛋白1、nephrin、podocin和synaptopodin。在病变肾小球中未检测到肾素mRNA和肾素蛋白。这些发现提供了初步证据，表明肾素谱系细胞可以作为肾小球上皮细胞的祖细胞，在以足细胞耗竭为特征的肾小球疾病中促进肾小球再生。
Glomerular injury Leads to podocyte Loss, a process directly underlying progressive glomerular scarring and decline of kidney function. The inherent repair process is limited by the inability of podocytes to regenerate. Cells of renin lineage residing alongside glomerular capillaries are reported to have progenitor capacity. We investigated whether cells of renin lineage can repopulate the glomerulus after podocyte injury and serve as glomerular epithelial cell progenitors. Kidney cells expressing renin were genetically fate-mapped in adult Ren1cCreER x Rs-tdTomato-R, Ren1cCre x Rs-ZsGreen-R, and Ren1dCre x Z/EG reporter mice. Podocyte depletion was induced in all three cell-specific reporter mice by cytotoxic anti-podocyte antibodies. After a decrease in podocyte number, a significant increase in the number of labeled cells of renin Lineage was observed in glomeruli in a focal distribution along Bowman's capsule, within the glomerular tuft, or in both locations. A subset of cells lining Bowman's capsule activated expression of the glomerular parietal epithelial cell markers paired box protein PAX2 and claudin-1. A subset of Labeled cells within the glomerular tuft expressed the podocyte markers Wilms tumor protein 1, nephrin, podocin, and synaptopodin. Neither renin mRNA nor renin protein was detected de novo in diseased glomeruli. These findings provide initial evidence that cells of renin Lineage may enhance glomerular regeneration by serving as progenitors for glomerular epithelial cells in glomerular disease characterized by podocyte depletion.