Ehara T, Carone F A, McCarthy K J, Couchman J R
Department of Cell Biology, University of Alabama at Birmingham 35294-0019.
Am J Pathol. 1994 Mar;144(3):612-21.
Alterations in basement membrane components, notably proteoglycans, in a rat model of polycystic kidney disease have been investigated. Rats were fed phenol II (2-amino-4-hydroxyphenyl-5-phenyl thiazole) for 4 days and then changed to normal diet for a 7-day recovery period. Marked dilation of distal tubules and collecting ducts was observed by 4 days with phenol II treatment, but the morphology returned to normal after 7 days of subsequent normal diet. Staining of tissue sections with two mouse monoclonal antibodies to a recently described basement membrane chondroitin sulfate proteoglycan (BM-CSPG) core protein was markedly diminished in the basement membranes of dilated cystic tubules. Reduction in staining was evident as early as 2 days. During recovery, BM-CSPG increased in tubular basement membranes and returned to normal after 7 days. Staining with a polyclonal antibody to chondroitin sulfate chains confirmed these changes in cystic tubule basement membranes. During the recovery stage, interstitial chondroitin sulfate (representing a CSPG other than BM-CSPG) was greatly increased around these tubules, along with the glycoprotein fibronectin. Staining with antibody to a basement membrane heparan sulfate proteoglycan core protein related to perlecan did not diminish but rather stained affected tubules intensely, whereas laminin, on the other hand, was apparently diminished in the basement membranes of the cystic tubules. Type IV collagen staining did not change through disease onset or recovery. These results suggest that BM-CSPG, which was rapidly altered in distribution through the onset and recovery phases, may be a sensitive marker of the cystic state, and in addition, the expression of basement membrane proteoglycans may be specifically and separately regulated in this disease.
在多囊肾病大鼠模型中，已对基底膜成分（尤其是蛋白聚糖）的改变进行了研究。给大鼠喂食苯酚II（2-氨基-4-羟基苯基-5-苯基噻唑）4天，然后改为正常饮食，进行为期7天的恢复期。苯酚II处理4天后，观察到远端小管和集合管明显扩张，但在随后7天的正常饮食后，形态恢复正常。用两种针对最近描述的基底膜硫酸软骨素蛋白聚糖（BM-CSPG）核心蛋白的小鼠单克隆抗体对组织切片进行染色，在扩张的囊性小管的基底膜中明显减少。早在2天时，染色减少就很明显。在恢复过程中，BM-CSPG在肾小管基底膜中增加，并在7天后恢复正常。用针对硫酸软骨素链的多克隆抗体染色证实了囊性小管基底膜中的这些变化。在恢复阶段，间质硫酸软骨素（代表除BM-CSPG之外的一种CSPG）在这些小管周围大量增加，同时糖蛋白纤连蛋白也增加。用针对与基底膜硫酸乙酰肝素蛋白聚糖核心蛋白相关的基底膜蛋白聚糖核心蛋白的抗体染色没有减少，反而使受影响的小管强烈染色，而另一方面，层粘连蛋白在囊性小管的基底膜中明显减少。IV型胶原染色在疾病发作或恢复过程中没有变化。这些结果表明，BM-CSPG在疾病发作和恢复阶段分布迅速改变，可能是囊性状态的敏感标志物，此外，基底膜蛋白聚糖的表达在这种疾病中可能受到特异性和单独的调节。
