Zhang Y Z, Lee H S
Department of Pathology, Seoul National University College of Medicine, Korea.
J Pathol. 1997 Sep;183(1):8-15. doi: 10.1002/(SICI)1096-9896(199709)183:1<8::AID-PATH1079>3.0.CO;2-W.
In membranous nephropathy (MN), the glomerular basement membrane (GBM) is thickened due to accumulation of GBM material between and around the subepithelial immune deposits. Alterations in the GBM components in relation to subepithelial deposits and GBM thickening are not clearly defined. The GBM distribution of classical and novel [alpha 4(IV)] chains of type IV collagen, laminin, and fibronectin have been studied in seven patients with MN and in three normal controls by a quantitative immunogold technique. In normal kidneys, the labelling of type IV collagen or fibronectin was distributed predominantly along the endothelial side of the GBM; alpha 4(IV) was found in the lamina densa; and laminin was concentrated in the epithelial zone of the GBM (P < 0.01). In MN, there were increased immunogold densities for classical and novel type IV collagen chains, laminin, and fibronectin in the spikes of MN patients compared with controls (P < 0.05). Furthermore, gold particle labelling for the alpha 4(IV) collagen chain was increased in the middle zone (P < 0.01) and that for fibronectin was increased in the endothelial and middle zones of the GBM (P < 0.05) compared with normal controls. These findings suggest that subepithelial immune deposits stimulate glomerular epithelial cells (GEC), resulting in enhanced secretion of classical and novel type IV collagen chains, laminin, and fibronectin, forming spikes in MN; of these newly formed components, only novel type IV collagen appears to migrate towards the middle zone of the GBM, contributing to thickening of this zone. The results also suggest that fibronectin, possibly derived from the circulation, is related to thickening of the endothelial zone of the GBM, which in turn might be related to progressive glomerulosclerosis.
在膜性肾病（MN）中，由于上皮下免疫沉积物之间及周围肾小球基底膜（GBM）物质的积聚，肾小球基底膜会增厚。与上皮下沉积物和GBM增厚相关的GBM成分改变尚未明确界定。通过定量免疫金技术，对7例MN患者和3例正常对照者的IV型胶原、层粘连蛋白和纤连蛋白的经典及新型[α4(IV)]链的GBM分布进行了研究。在正常肾脏中，IV型胶原或纤连蛋白的标记主要分布在GBM的内皮侧；α4(IV)位于致密层；层粘连蛋白集中在GBM的上皮区（P < 0.01）。在MN中，与对照组相比，MN患者钉突中经典及新型IV型胶原链、层粘连蛋白和纤连蛋白的免疫金密度增加（P < 0.05）。此外，与正常对照相比，α4(IV)胶原链的金颗粒标记在中间区增加（P < 0.01），纤连蛋白的金颗粒标记在GBM的内皮区和中间区增加（P < 0.05）。这些发现表明，上皮下免疫沉积物刺激肾小球上皮细胞（GEC），导致经典及新型IV型胶原链、层粘连蛋白和纤连蛋白的分泌增加，在MN中形成钉突；在这些新形成的成分中，只有新型IV型胶原似乎向GBM的中间区迁移，导致该区域增厚。结果还表明，可能来源于循环的纤连蛋白与GBM内皮区增厚有关，而这反过来可能与进行性肾小球硬化有关。
