Renal Division, Washington University School of Medicine, St. Louis, MO, USA.
Transl Res. 2012 Oct;160(4):291-7. doi: 10.1016/j.trsl.2012.03.004. Epub 2012 Apr 10.
The glomerular basement membrane (GBM) is lined by fenestrated endothelium from the capillary-lumen side and by interdigitating foot processes of the podocytes from the urinary- space side. These three layers of the glomerular capillary wall constitute the functional unit of the glomerular filtration barrier. The GBM is assembled through an interweaving of type IV collagen with laminins, nidogen, and sulfated proteoglycans. Mutations in genes encoding LAMB2, COL4A3, COL4A4, and COL4A5 cause glomerular disease in humans as well as in mice. In addition, laminin α5 mutation in podocytes leads to proteinuria and renal failure in mice. Moreover, more neoepitopes in Goodpasture's disease and for the first time alloepitopes in Alport post-transplantation nephritis have been located in the collagen α5(IV) NC1 domain. These discoveries underscore the importance of the GBM in establishing and maintaining the integrity of the glomerular filtration barrier.
肾小球基底膜（GBM）从毛细血管腔侧由有孔的内皮细胞排列，从尿腔侧由足细胞的足突相互穿插排列。肾小球毛细血管壁的这三层构成了肾小球滤过屏障的功能单位。GBM 通过 IV 型胶原与层粘连蛋白、巢蛋白和硫酸乙酰肝素蛋白聚糖的交织组装而成。编码 LAMB2、COL4A3、COL4A4 和 COL4A5 的基因突变在人类和小鼠中引起肾小球疾病。此外，足细胞中层粘连蛋白 α5 的突变导致小鼠蛋白尿和肾衰竭。此外，在 Goodpasture 病中首次定位到了新的表位，在移植后肾炎的 Alport 中也定位到了同种异体表位，它们都位于胶原 α5(IV)NC1 结构域。这些发现强调了 GBM 在建立和维持肾小球滤过屏障完整性方面的重要性。
