Jalanko H, Patrakka J, Tryggvason K, Holmberg C
Hospital for Children and Adolescents and Biomedicum Helsinki, University of Helsinki, Finland.
Ann Med. 2001 Nov;33(8):526-33. doi: 10.3109/07853890108995962.
The sieving of plasma components occurs in the kidney through the glomerular capillary wall. This filter is composed of three layers: endothelium, glomerular basement membrane (GBM), and podocyte foot processes connected by slit diaphragms. Defects in this barrier lead to proteinuria and nephrotic syndrome. Previously, defective GBM was regarded to be responsible for proteinuria. However, recent work on genetic diseases has indicated that podocytes and the slit diaphragm are crucial in restricting protein leakage. Congenital nephrotic syndrome of the Finnish type (NPHS1) is caused by mutations in a novel NPHS1 gene, which encodes for a cell adhesion protein, nephrin. This protein is synthesized by podocytes, and seems to be a major component of the slit diaphragm. In severe NPHS1, lack of nephrin leads to missing slit diaphragm. The role of nephrin in acquired kidney diseases remains unknown. In addition to nephrin, other podocyte proteins (podocin, alpha-actinin-4, CD2AP, FAT) have recently been identified and associated with the development of proteinuria. It seems that the slit diaphragm and its interplay with the podocyte cytoskeleton is critical for the normal sieving process, and defects in one of these components easily lead to proteinuria.
血浆成分的筛滤在肾脏中通过肾小球毛细血管壁进行。这个滤器由三层组成：内皮、肾小球基底膜（GBM）以及通过裂孔隔膜相连的足细胞足突。该屏障的缺陷会导致蛋白尿和肾病综合征。以前，人们认为GBM缺陷是蛋白尿的原因。然而，最近关于遗传疾病的研究表明，足细胞和裂孔隔膜在限制蛋白质渗漏方面至关重要。芬兰型先天性肾病综合征（NPHS1）由一个新的NPHS1基因突变引起，该基因编码一种细胞黏附蛋白——nephrin。这种蛋白质由足细胞合成，似乎是裂孔隔膜的主要成分。在严重的NPHS1中，nephrin的缺乏导致裂孔隔膜缺失。nephrin在获得性肾脏疾病中的作用仍然未知。除了nephrin，最近还发现了其他足细胞蛋白（podocin、α-辅肌动蛋白-4、CD2AP、FAT），它们与蛋白尿的发生有关。似乎裂孔隔膜及其与足细胞细胞骨架的相互作用对于正常的筛滤过程至关重要，这些成分中的任何一个出现缺陷都容易导致蛋白尿。
