Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia
Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia
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DOI：
10.1093/ndt/gfl711
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发表时间：
2007-04-01
影响因子：
6.1
通讯作者：
Grande, Joseph P.
中科院分区：
文献类型：
--
作者：
Garovic, Vesna D.;Wagner, Steven J.;Grande, Joseph P.
背景。子痫前期是一种以高血压和蛋白尿为特征的妊娠特异性疾病。在其他疾病状态下，蛋白尿与足细胞足突蛋白的表达改变有关，但尚未在先兆子痫妇女中进行研究。我们试图验证子痫前期蛋白尿与足细胞骨架和/或紧密连接蛋白的表达失调有关的假设。从尸检材料中获得了7名妇女的肾组织，这些妇女在怀孕后半期至分娩后48小时内患有严重的先兆子痫，随后死亡。作为对照，我们使用了两名在正常怀孕后半期意外死亡的妇女的尸检材料。免疫组化染色对石蜡包埋材料的代表性切片进行nephrin、synaptopodin和podocin的检测。与对照组相比，子痫前期肾组织中nephrin和synaptopodin的表达均明显降低。相比之下，病例和对照组均表现出强烈的podocin染色。我们得出结论，nephrin和synaptopodin的下调与子痫前期妇女蛋白尿有关。最近的研究表明，与正常妊娠相比，子痫前期的可溶性血管内皮生长因子受体1 （sFlt-1）水平升高。小鼠研究表明，sFlt-1可能通过中和血管内皮生长因子（VEGF）和抑制肾素在诱导蛋白尿中发挥作用。子痫前期的蛋白尿和sFlt-1的升高具有时间相关性，进一步支持了sFlt-1在足细胞足突蛋白失调中的可能作用。
Background. Preeclampsia is a pregnancy-specific disorder characterized by hypertension and proteinuria. In other disease states, proteinuria has been linked to altered expressions of podocyte foot-process proteins, but this has not been studied in women with preeclampsia. We sought to test the hypothesis that proteinuria in preeclampsia is associated with dysregulated expression of the podocyte cytoskeleton and/or tight junction proteins.Mathods. Renal tissue was obtained from autopsy material from seven women who had severe preeclampsia during the second half of their pregnancies up to 48 h after delivery, and who subsequently died. As controls, we used autopsy material from two women who died accidentally during the second half of their otherwise normal pregnancies. Immunohistochemical stains for nephrin, synaptopodin and podocin were performed on representative sections prepared from paraffin-embedded material.Results. Expression of both nephrin and synaptopodin was markedly decreased in preeclamptic compared with control kidney sections. By contrast, both cases and controls demonstrated strong staining for podocin.Conclusions. We conclude that down-regulation of nephrin and synaptopodin is associated with proteinuria in women with preeclampsia. Recent studies have demonstrated that soluble vascular endothelial growth factor receptor 1 (sFlt-1) levels are elevated in preeclampsia compared with normal pregnancy. Studies in mice have shown that sFlt-1 may play a role in inducing proteinuria by neutralizing vascular endothelial growth factor (VEGF) and suppressing nephrin. Proteinuria and elevations of sFlt-1 in preeclampsia are temporally related, further supporting a possible role of sFlt-1 in the dysregulation of podocyte foot-process proteins.