Proteinuria with and without renal glomerular podocyte effacement
Proteinuria with and without renal glomerular podocyte effacement
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DOI：
10.1681/asn.2006060628
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发表时间：
2006-09-01
影响因子：
13.6
通讯作者：
Kalluri, Raghu
中科院分区：
文献类型：
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作者：
Kalluri, Raghu
蛋白尿和肾脏疾病患者的肾活检最常与足细胞足突消失有关。几十年来，肾病学家一直想知道蛋白尿是足细胞足突消失的结果还是原因。在过去的几年里，作者的实验室使用了不同的蛋白尿小鼠模型来解决这个问题。虽然在大多数情况下，足细胞消失与蛋白尿和肾小球疾病有关，但在三种不同的小鼠模型中，已经证明在足细胞足突消失的情况下也可以观察到蛋白尿。第一种模型是通过注射抗血管内皮生长因子或可溶性血管内皮生长因子受体1的抗体而产生的。第二种模型是肾小球基底膜IV型胶原α3链缺失的小鼠。第三种模型是由一种名为neaffin的狭缝横隔膜蛋白的基因缺失产生的。总而言之，这些实验和几项人类研究的支持证据表明，肾小球基底膜或肾小球内皮细胞的严重缺陷可以导致蛋白尿，而不会导致足突消失。
Renal biopsies of patients with proteinuria and kidney disease most often are associated with podocyte foot process effacement. For several decades, nephrologists have wondered whether proteinuria is a result of podocyte foot process effacement or the cause of it. In the past few years, the author's laboratory has addressed this issue using different mouse models of proteinuria. Although in most cases, podocyte effacement is associated with proteinuria and glomerular disease, in three different mouse models, it was demonstrated that proteinuria can be observed without podocyte foot process effacement. The first model is generated by injection of antibodies to vascular endothelial growth factor or soluble vascular endothelial growth factor receptor 1. The second model is a mouse with deletion of type IV collagen alpha 3 chain in the glomerular basement membrane. The third model was generated by genetic deletion of a slit diaphragm protein known as nephrin. Collectively, these experiments and the supporting evidence from several human studies demonstrate that severe defects in either the glomerular basement membrane or the glomerular endothelium can lead to proteinuria without foot process effacement.