Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Nephron Exp Nephrol. 2013;124(3-4):11-8. doi: 10.1159/000357356. Epub 2014 Jan 8.
BACKGROUND/AIMS: Recent study suggests that activation of parietal epithelial cells (PECs) contributes to pathogenesis of glomerulosclerosis and the activation marker CD44 increases in evolving glomerulosclerosis. Here we examined the pathogenic roles of CD44+ epithelial cells in mouse adriamycin nephropathy (ADRN), a representative rodent model for idiopathic focal segmental glomerulosclerosis (FSGS). We also evaluated whether the prevalence of CD44+ PECs reflects different levels of podocyte injuries.
As a model of FSGS with different degrees of podocyte injury, ADRN models in mice of different ages were utilized. Immunohistochemistry and immunofluorescence were used to determine roles of CD44 expression.
By immunohistochemistry, CD44 expression became positive in claudin-1+ PECs and an increase in CD44+ PECs was associated with reduced expression of synaptopodin and podocin in diseased glomeruli. Furthermore, immunofluorescence staining demonstrated co-expression with osteopontin, a CD44 ligand that plays a significant role in the progression of glomerulosclerosis, thereby suggesting interactions between these molecules. Analysis of the number of WT-1+ podocytes and the levels of electron microscopic foot process effacement revealed a milder degree of podocyte injury in younger ADRN models compared to older ones. Comparative immunohistochemical analysis indicated that the prevalence of CD44+ PECs consistently reflects different degrees of podocyte injury within each different-aged ADRN model.
CD44+ PECs play significant roles in progressive glomerulosclerosis and the prevalence of the cells reflects different degrees of podocyte injury in ADRN.
背景/目的：最近的研究表明，顶泌上皮细胞（PECs）的激活有助于肾小球硬化的发病机制，并且在进行性肾小球硬化中，激活标志物 CD44 增加。在这里，我们研究了 CD44+上皮细胞在小鼠阿霉素肾病（ADRN）中的致病作用，ADRN 是特发性局灶节段性肾小球硬化（FSGS）的代表性啮齿动物模型。我们还评估了 CD44+PEC 的流行率是否反映了不同程度的足细胞损伤。
作为具有不同程度足细胞损伤的 FSGS 模型，利用了不同年龄的 ADRN 模型小鼠。使用免疫组织化学和免疫荧光法确定 CD44 表达的作用。
通过免疫组织化学， Claudin-1+PEC 中 CD44 的表达呈阳性，并且 CD44+PEC 的增加与病变肾小球中 synaptopodin 和 podocin 的表达减少有关。此外，免疫荧光染色显示与骨桥蛋白共表达，骨桥蛋白是一种在肾小球硬化进展中起重要作用的 CD44 配体，从而表明这些分子之间存在相互作用。WT-1+足细胞数量和电子显微镜足突消失程度的分析表明，与年龄较大的 ADRN 模型相比，年龄较小的 ADRN 模型中的足细胞损伤程度较轻。比较免疫组织化学分析表明，在每个不同年龄的 ADRN 模型中，CD44+PEC 的流行率始终反映了不同程度的足细胞损伤。
CD44+PEC 在进行性肾小球硬化中起重要作用，并且细胞的流行率反映了 ADRN 中足细胞损伤的不同程度。
