Neuronal proteins are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation
Neuronal proteins are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation
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DOI：
10.1038/ki.2012.321
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发表时间：
2013-01-01
影响因子：
19.6
通讯作者：
Patrakka, Jaakko
中科院分区：
文献类型：
--
作者：
Sistani, Laleh;Rodriguez, Patricia Q.;Patrakka, Jaakko
足细胞在肾小球滤过屏障中起中心作用，其典型特征是高度组织化的初级(主要)和次级(足部)突起的复杂形态。足部突起的分子组成已经很好地描述了，但主要突起的分子组成却鲜为人知。在此之前，我们通过大规模测序和微阵列分析对肾小球转录组进行了分析。出乎意料的是，调查发现三种神经元蛋白(亨廷顿相互作用蛋白1(Hip1)、神经筋膜蛋白(NFasc)和嗅觉素样蛋白2a(Olfml2a))在肾小球中表达丰富。这些蛋白仅由足细胞表达，经RT-PCR、免疫印迹、免疫荧光和免疫电子显微镜证实，它们定位于主要突起。在足细胞发育过程中，这些蛋白与波形蛋白共存，证实了它们与主要过程的关联。应用免疫组织化学方法，我们发现Hip1和Olfml2a以及公认的足细胞标记物Synaptopodin和Pdlim2在人肾小球新月体中共表达，表明这些病变中存在足细胞。因此，三种神经元蛋白在足细胞主突中高度表达。使用这些新的标记物，我们发现足细胞有助于肾小球新月体的形成。《国际肾脏》(2012年)83，63-71；doi：10.1038/ki.2012.321；2012年8月22日在线发布
The podocyte has a central role in the glomerular filtration barrier typified by a sophisticated morphology of highly organized primary (major) and secondary (foot) processes. The molecular makeup of foot processes is well characterized, but that of major processes is poorly known. Previously, we profiled the glomerular transcriptome through large-scale sequencing and microarray profiling. Unexpectedly, the survey found expression of three neuronal proteins (Huntingtin interacting protein 1 (Hip1), neurofascin (Nfasc), and olfactomedin-like 2a (Olfml2a)), all enriched in the glomerulus. These proteins were expressed exclusively by podocytes, wherein they localized to major processes as verified by RT-PCR, western blotting, immunofluorescence, and immunoelectron microscopy. During podocyte development, these proteins colocalized with vimentin, confirming their association with major processes. Using immunohistochemistry, we found coexpression of Hip1 and Olfml2a along with the recognized podocyte markers synaptopodin and Pdlim2 in glomerular crescents of human kidneys, indicating the presence of podocytes in these lesions. Thus, three neuronal proteins are highly expressed in podocyte major process. Using these new markers we found that podocytes contribute to the formation of glomerular crescents. Kidney International (2012) 83, 63-71; doi:10.1038/ki.2012.321; published online 22 August 2012