Van den Heuvel L P, Van den Born J, Jalanko H, Schröder C H, Veerkamp J H, Assmann K J, Berden J H, Holmberg C, Rapola J, Monnens L A
Department of Biochemistry, University of Nijmegen, The Netherlands.
Pediatr Nephrol. 1992 Jan;6(1):10-5. doi: 10.1007/BF00856820.
A decrease in the concentration of heparan sulphate proteoglycan (HSPG) in the glomerular basement membrane (GBM) is supposed to cause the increased GBM permeability in the congenital nephrotic syndrome (CNS). Therefore, we analysed the glycosaminoglycan (GAG) content and composition of the GBM and tubular basement membrane (TBM) from 3 patients with CNS of the Finnish type (FCNS) and 16 control infants. The GAG content, determined by spectrophotometric assay after papain digestion, was not significantly different in FCNS patients compared with controls. In addition, the GAG composition was comparable in the two groups, with heparan sulphate (HS) constituting at least 75% of the total GAG content. The urinary GAG content (expressed as mg GAG/mmol creatinine) was age dependent, but similar in both groups. Indirect immunofluorescence studies on kidney tissue from normal human infants, using monoclonal or polyclonal antibodies against the core protein of human GBM HSPG, showed linear staining of almost all renal basement membranes. A monoclonal antibody directed against the HS chain of HSPG showed strong GBM and a weak TBM staining. Kidney tissue from three patients with FCNS displayed no discernible differences in the distribution or quality of staining with the same antibodies. These biochemical and immunohistochemical results are in contrast to the decrease in anionic sites (by polyethyleneimine staining) and the replacement of GBM HS by chondroitin sulphate, observed by others in CNS of the diffuse mesangial sclerosis type.
肾小球基底膜（GBM）中硫酸乙酰肝素蛋白聚糖（HSPG）浓度降低被认为会导致先天性肾病综合征（CNS）中GBM通透性增加。因此，我们分析了3例芬兰型先天性肾病综合征（FCNS）患者和16例对照婴儿的肾小球基底膜（GBM）及肾小管基底膜（TBM）的糖胺聚糖（GAG）含量和组成。经木瓜蛋白酶消化后用分光光度法测定的GAG含量，FCNS患者与对照组相比无显著差异。此外，两组的GAG组成相当，硫酸乙酰肝素（HS）占总GAG含量的至少75%。尿GAG含量（以mg GAG/mmol肌酐表示）与年龄有关，但两组相似。使用针对人GBM HSPG核心蛋白的单克隆或多克隆抗体对正常人类婴儿肾组织进行间接免疫荧光研究，结果显示几乎所有肾基底膜均呈线性染色。一种针对HSPG的HS链的单克隆抗体显示GBM染色强而TBM染色弱。3例FCNS患者的肾组织在用相同抗体染色时，在分布或染色质量上未显示出明显差异。这些生化和免疫组化结果与其他人在弥漫性系膜硬化型CNS中观察到的阴离子位点减少（通过聚乙烯亚胺染色）以及GBM HS被硫酸软骨素替代的情况形成对比。
