Tryggvason K, Wartiovaara J
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Curr Opin Nephrol Hypertens. 2001 Jul;10(4):543-9. doi: 10.1097/00041552-200107000-00009.
Recent discoveries in kidney research have given new insights into the molecular make-up of the glomerular filter and mechanisms of permselectivity. The identification of mutations in the genes for glomerular basement membrane type IV collagen has thus demonstrated the central role of the glomerular basement membrane as the structural skeleton of the glomerular capillary. Regional deterioration of this framework not only leads to proteinuria, but also to significant leakage of red blood cells into the urinary space. Tracer studies and the characterization of other glomerular basement membrane components, such as proteoglycans, have also emphasized the role of the glomerular basement membrane in the permselectivity process. However, more recent studies on nephrin, a key component of the slit diaphragm, as well as the podocyte and slit diaphragm-associated intracellular proteins, CD2-associated protein, podocin and alpha-actinin-4, have emphasized the role of the slit diaphragm as a central size-selective filtration barrier. These data have provided a completely new understanding of the mechanisms of proteinuria, both in inherited and acquired diseases. In this review, we present the recent progress made in the characterization of proteins that are important for glomerular permselectivity.
肾脏研究领域的最新发现为肾小球滤过器的分子组成和选择通透性机制提供了新的见解。肾小球基底膜IV型胶原蛋白基因突变的鉴定表明，肾小球基底膜作为肾小球毛细血管的结构骨架发挥着核心作用。该框架的局部退化不仅会导致蛋白尿，还会导致红细胞大量漏入尿腔。示踪研究以及对其他肾小球基底膜成分（如蛋白聚糖）的表征，也强调了肾小球基底膜在选择通透性过程中的作用。然而，最近对裂孔隔膜的关键成分nephrin以及足细胞和与裂孔隔膜相关的细胞内蛋白（CD2相关蛋白、足突蛋白和α-辅肌动蛋白-4）的研究，强调了裂孔隔膜作为核心的大小选择性滤过屏障的作用。这些数据为遗传性和获得性疾病中蛋白尿的机制提供了全新的认识。在这篇综述中，我们介绍了在对肾小球选择通透性重要的蛋白质表征方面取得的最新进展。
