The Proximal Tubule and Albuminuria: Really!
The Proximal Tubule and Albuminuria: Really!
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DOI：
10.1681/asn.2013090950
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发表时间：
2014-03-01
影响因子：
13.6
通讯作者：
Molitoris, Bruce A.
中科院分区：
文献类型：
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作者：
Dickson, Landon E.;Wagner, Mark C.;Molitoris, Bruce A.
最近的数据强调了近端小管（PT）在肾小球滤液中尿白蛋白的再吸收、处理和转细胞化中的作用。创新的技术和方法为这些过程提供了令人兴奋的见解，许多研究者已经表明，选择性PT细胞缺陷导致显著的蛋白尿，甚至在动物模型中达到肾病的范围。因此，白蛋白重吸收和胞吞作用的机制正在进行深入的研究。新生儿Fc受体（FcRn）与巨噬蛋白和立方蛋白（一种非选择性多受体复合物，主要指导溶酶体降解蛋白）协同作用，位于顶端膜刷状边界的新生儿Fc受体（FcRn）被认为是介导白蛋白转胞作用的受体。FcRn通路促进重吸收，并通过其ph依赖性结合亲和力介导胞吞作用。这也允许选择性白蛋白分选在PT细胞内。这种回收途径最大限度地减少尿损失和白蛋白的分解代谢，从而延长其血清半衰期。它也可以作为一种分子分选器来保存和回收正常的白蛋白，同时允许改变的白蛋白通过溶酶体途径被分解代谢。在这里，我们批判性地回顾了支持这种新机制的数据。
Recent data highlight the role of the proximal tubule (PT) in reabsorbing, processing, and transcytosing urinary albumin from the glomerular filtrate. Innovative techniques and approaches have provided exciting insights into these processes, and numerous investigators have shown that selective PT cell defects lead to significant albuminuria, even reaching nephrotic range in animal models. Thus, the mechanisms of albumin reabsorption and transcytosis are undergoing intense study. Working in concert with megalin and cubilin, a nonselective multireceptor complex that predominantly directs proteins for lysosomal degradation, the neonatal Fc receptor (FcRn) located at the brush border of the apical membrane has been implicated as the receptor mediating albumin transcytosis. The FcRn pathway facilitates reabsorption and mediates transcytosis by its pH-dependent binding affinity in endosomal compartments. This also allows for selective albumin sorting within the PT cell. This reclamation pathway minimizes urinary losses and catabolism of albumin, thus prolonging its serum half-life. It may also serve as a molecular sorter to preserve and reclaim normal albumin while allowing altered albumin to be catabolized via lysosomal pathways. Here, we critically review the data supporting this novel mechanism.