Fogel M A, Boyd C D, Leardkamolkarn V, Abrahamson D R, Minto A W, Salant D J
Evans Memorial Department of Clinical Research, Boston University Medical Center, Massachusetts.
Am J Pathol. 1991 Feb;138(2):465-75.
The distribution and synthetic rate of glomerular basement membrane components was examined in the Passive Heymann Nephritis model of experimental membranous nephropathy. The extensive tissue injury that developed included subepithelial electron-dense deposits, podocyte foot process effacement, and expansion of the glomerular basement membrane. Levels of mRNA for type IV collagen, laminin, and fibronectin from isolated glomeruli was quantitated by slot-blot analysis and showed no change in experimental animals as compared to controls at either 1 week, 3 weeks, or 3 months after disease induction. Immunoelectron microscopy with gold-labeled anti-laminin IgG revealed no difference in the number of particles bound to the glomerular basement membrane of experimental animals and controls. Immunofluorescence with both type IV collagen antisera and anti-laminin antibody showed no difference in the intensity or pattern of staining. Despite extensive glomerular damage and glomerular basement membrane thickening, no evidence was found for either an increase in the synthetic rate of type IV collagen, laminin, or fibronectin or for an accumulation of basement membrane laminin within the damaged glomeruli. Alternate processes, such as diminished density of matrix components or accumulation of other unmeasured matrix constituents, presumably account for the expansion of the glomerular basement membrane seen in experimental membranous nephropathy.
在实验性膜性肾病的被动海曼肾炎模型中,研究了肾小球基底膜成分的分布和合成速率。所发生的广泛组织损伤包括上皮下电子致密沉积物、足细胞足突消失以及肾小球基底膜增厚。通过狭缝印迹分析对分离的肾小球中IV型胶原、层粘连蛋白和纤连蛋白的mRNA水平进行定量,结果显示,在疾病诱导后1周、3周或3个月时,与对照组相比,实验动物的这些mRNA水平没有变化。用金标记的抗层粘连蛋白IgG进行免疫电子显微镜检查发现,实验动物和对照组肾小球基底膜上结合的颗粒数量没有差异。用IV型胶原抗血清和抗层粘连蛋白抗体进行免疫荧光检查显示,染色强度或模式没有差异。尽管肾小球有广泛损伤和肾小球基底膜增厚,但未发现IV型胶原、层粘连蛋白或纤连蛋白的合成速率增加,也未发现受损肾小球内基底膜层粘连蛋白的积累。其他过程,如基质成分密度降低或其他未测定的基质成分积累,可能是实验性膜性肾病中所见肾小球基底膜增厚的原因。