Kawachi Hiroshi, Koike Hiroko, Shimizu Fujio
Department of Cell Biology, Institute of Nephrology, Faculty of Medicine, Niigata University, Niigata 951-8510. Japan.
Microsc Res Tech. 2002 May 15;57(4):236-40. doi: 10.1002/jemt.10081.
It is well established that the glomerular capillary wall consists of three layers: endothelial cell, glomerular basement membrane, and the slit diaphragm bridging foot processes of glomerular epithelial cell. Which structure in the glomerular capillary wall represents the primary filter for retaining plasma proteins is not clearly elucidated. An anti-slit diaphragm monoclonal antibody (mAb) 5-1-6 causes massive proteinuria in rats by single intravenous injection, which clearly indicates that the slit diaphragm plays a critical role for maintaining the barrier function of the glomerular capillary wall. Recently, we concluded that mAb 5-1-6 recognized a rat homolog of nephrin, a gene product of NPHS1. The expression of nephrin decreased in puromycin aminonucleoside nephropathy and adriamycin nephropathy as well as mAb 5-1-6-induced nephropathy, which suggested that nephrin was involved in the development of proteinuria in these proteinuric states. In mAb 5-1-6 nephropathy, the slit diaphragm was maintained morphologically normal, although nephrin expression dramatically decreased. The finding suggested that nephrin was not a sole component of the slit diaphragm. To better understand the structure of the slit diaphragm, it is particularly important to identify other components that build up the structure of the slit diaphragm together with nephrin.
肾小球毛细血管壁由三层组成，即内皮细胞、肾小球基底膜以及连接肾小球上皮细胞足突的裂孔隔膜，这一点已得到充分证实。肾小球毛细血管壁中哪个结构是保留血浆蛋白的主要滤过屏障尚不清楚。抗裂孔隔膜单克隆抗体（mAb）5-1-6通过单次静脉注射可使大鼠出现大量蛋白尿，这清楚地表明裂孔隔膜在维持肾小球毛细血管壁的屏障功能中起关键作用。最近，我们得出结论，mAb 5-1-6识别的是NPHS1基因产物nephrin的大鼠同源物。在嘌呤霉素氨基核苷肾病、阿霉素肾病以及mAb 5-1-6诱导的肾病中，nephrin的表达均降低，这表明nephrin参与了这些蛋白尿状态下蛋白尿的发生发展。在mAb 5-1-6肾病中，尽管nephrin表达显著降低，但裂孔隔膜在形态上保持正常。这一发现表明nephrin并非裂孔隔膜的唯一组成成分。为了更好地理解裂孔隔膜的结构，识别与nephrin共同构成裂孔隔膜结构的其他成分尤为重要。
