Compound effects of aging and experimental FSGS on glomerular epithelial cells.
Compound effects of aging and experimental FSGS on glomerular epithelial cells.
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DOI：
10.18632/aging.101176
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发表时间：
2017-02-17
期刊：
影响因子：
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通讯作者：
Shankland SJ
中科院分区：
文献类型：
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作者：
Schneider RR;Eng DG;Kutz JN;Sweetwyne MT;Pippin JW;Shankland SJ
高龄预示着FSGS的预后较差。为了了解年龄对肾小球足细胞和壁上皮细胞（PECs）的影响，我们在300万岁小鼠（人类年龄20岁）和2700万岁小鼠（人类年龄78岁）中，通过使用细胞病变抗足细胞抗体突然消耗足细胞来诱导实验性FSGS。尽管有类似的疾病诱导抗体结合，老年FSGS小鼠的足细胞密度比年轻FSGS小鼠低。与年轻FSGS小鼠相比，老年小鼠激活的PEC密度更高，总激活PEC的百分比也更高。此外，老年FSGS小鼠肾小球中含有ERK和EMT磷酸化的PECs的百分比更高。通过胶原IV和银染色测定，老年FSGS小鼠沿鲍曼囊的细胞外基质较高。然而，在年轻FSGS小鼠和老年FSGS小鼠中，单独肾小球簇和同时存在簇状和鲍曼囊积聚的肾小球中胶原IV的积累是相似的。因此，老龄小鼠FSGS胶原IV染色的主要差异是沿着鲍曼囊。年轻小鼠和老年小鼠FSGS足细胞、PECs和细胞外基质积累的显著差异可能解释了FSGS基于年龄的结果差异。
Advanced age portends a poorer prognosis in FSGS. To understand the impact of age on glomerular podocytes and parietal epithelial cells (PECs), experimental FSGS was induced in 3m-old mice (20-year old human age) and 27m-old mice (78-year old human age) by abruptly depleting podocytes with a cytopathic anti-podocyte antibody. Despite similar binding of the disease-inducing antibody, podocyte density was lower in aged FSGS mice compared to young FSGS mice. Activated PEC density was higher in aged versus young FSGS mice, as was the percentage of total activated PECs. Additionally, the percentage of glomeruli containing PECs with evidence of phosphorylated ERK and EMT was higher in aged FSGS mice. Extracellular matrix, measured by collagen IV and silver staining, was higher in aged FSGS mice along Bowman's capsule. However, collagen IV accumulation in the glomerular tufts alone and in glomeruli with both tuft and Bowman's capsule accumulation were similar in young FSGS and aged FSGS mice. Thus, the major difference in collagen IV staining in FSGS was along Bowman's capsule in aged mice. The significant differences in podocytes, PECs and extracellular matrixaccumulation between young mice and old mice with FSGS might explain the differences in outcomes in FSGS based on age.