The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy.
The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy.
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DOI：
10.1038/ki.2015.273
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发表时间：
2015-11
影响因子：
19.6
通讯作者：
Alpers CE
中科院分区：
文献类型：
--
作者：
Andeen NK;Nguyen TQ;Steegh F;Hudkins KL;Najafian B;Alpers CE
糖尿病肾病（DN）在人类和小鼠中已获得逆转，但仅在特殊情况下罕见。由于DN的进展与足细胞损失有关，因此DN的逆转需要足细胞的恢复。在这里，我们确定和量化潜在的肾小球祖细胞，可能是恢复足细胞的来源。在31例人肾活检病例中确定了DN，并将其分为形态学早期或晚期病变。免疫组化法检测足细胞（WT-1，p57）、壁上皮细胞（claudin-1）和细胞增殖（Ki-67）标志物。足细胞密度随着DN的进展而降低。对照组Bowman囊上很少出现标记为足细胞（p57）的细胞，但在组织学早期DN中显著增加。Ki-67表达细胞在DN的肾小球丛和Bowman囊上被鉴定，但在对照中很少。标记为佩奇的细胞存在于肾小球簇上，特别是在形态学晚期的DN中。这些结果显示足细胞和PEC群体中存在表型可塑性的证据，并且与BTBR ob/ob小鼠模型中的研究一致，其中DN的可逆性发生在足细胞可能从PEC前体再生的情况下。因此，我们的研究结果支持，但不能证明，足细胞可以再生从PEC祖细胞在人DN。如果是这样，DN的进展可能代表足细胞损失和再生之间的可改变的净平衡。
Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. Since progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (claudin-1) and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman's capsule in controls, but significantly increased in histologically early DN. Ki-67 expressing cells were identified on the glomerular tuft and Bowman's capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration.