Klingel R, Ramadori G, Schuppan D, Knittel T, Meyer zum Büschenfelde K H, Köhler H
First Department of Internal Medicine, University of Mainz, FRG.
Nephron. 1993;65(1):111-8. doi: 10.1159/000187451.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common entity of cystic diseases of the kidney leading to end-stage renal insufficiency. Changes in extracellular matrix (ECM) are regarded to be an important pathogenic factor connected with the genes assumed to be responsible for human ADPKD. In order to assess the biological significance of altered expression and deposition of ECM glycoproteins for human ADPKD at molecular levels fresh-frozen tissue from ADPKD kidneys, fetal kidneys and normal adult kidneys were comparatively tested by immunohistochemistry for the presence of multifunctional ECM glycoproteins undulin, tenascin and fibronectin, interstitial collagen types I, III and VI and intrinsic basement membrane components laminin and collagen type IV using monoclonal antibodies and polyclonal antisera. Studies were especially focused on ECM glycoproteins undulin and tenascin which in connection with interstitial collagens and fibronectin have specific structural and functional roles in tissue development and differentiation. Cultures of cyst-lining epithelial cells from two polycystic kidneys and autologous fibroblasts were investigated in vitro. By Northern blot analysis mRNA levels of undulin, tenascin and the ECM-regulating growth factor transforming growth factor-beta 1 (TGF-beta 1) were investigated. A strong increase of fibrogenesis was demonstrated in tissue architecture of polycystic kidneys. Immunohistochemically subepithelial fibrous tissue of cyst walls in ADPKD kidneys showed strong coexpression of both undulin and tenascin with marked intensity adjacent to cyst-lining epithelium. In contrast the normal adult human kidney and developmental stages of the fetal kidney showed expression patterns of undulin and tenascin which were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
常染色体显性多囊肾病（ADPKD）是导致终末期肾功能不全的最常见的肾囊性疾病。细胞外基质（ECM）的变化被认为是与假定导致人类ADPKD的基因相关的重要致病因素。为了在分子水平评估ECM糖蛋白表达和沉积改变对人类ADPKD的生物学意义，采用单克隆抗体和多克隆抗血清，通过免疫组织化学对来自ADPKD肾脏、胎儿肾脏和正常成人肾脏的新鲜冷冻组织进行比较检测，以确定多功能ECM糖蛋白内收蛋白、腱生蛋白和纤连蛋白、I型、III型和VI型间质胶原以及固有基底膜成分层粘连蛋白和IV型胶原的存在情况。研究特别关注与间质胶原和纤连蛋白相关的ECM糖蛋白内收蛋白和腱生蛋白，它们在组织发育和分化中具有特定的结构和功能作用。对来自两个多囊肾的囊肿衬里上皮细胞和自体成纤维细胞进行体外培养研究。通过Northern印迹分析研究内收蛋白、腱生蛋白和调节ECM的生长因子转化生长因子-β1（TGF-β1）的mRNA水平。结果表明多囊肾组织结构中纤维生成显著增加。免疫组织化学显示，ADPKD肾脏囊肿壁的上皮下纤维组织中，内收蛋白和腱生蛋白强烈共表达，在囊肿衬里上皮附近强度明显。相比之下，正常成人肾脏和胎儿肾脏的发育阶段显示出内收蛋白和腱生蛋白的表达模式有显著差异。（摘要截短于250字）
