McKee M D, Nanci A, Khan S R
Department of Stomatology, Faculty of Dentistry, Université de Montréal, QC, Canada.
J Bone Miner Res. 1995 Dec;10(12):1913-29. doi: 10.1002/jbmr.5650101211.
The organic matrix of renal calculi has long been considered to influence the crystal growth that occurs in these pathological mineral deposits. Recent advances in characterizing individual organic moieties from mineralized tissues in general and the combined use of antibodies raised against these molecules with different immunocytochemical approaches have allowed their precise distribution to be visualized in a variety of normal and pathological mineralized tissues. The present ultrastructural study reports on the epithelial expression and extracellular localization of several noncollagenous proteins in rat and human kidney stones using high-resolution colloidal-gold immunocytochemistry. To this end, we have examined in an ethylene glycol-induced calcium oxalate model of urolithiasis in the rat, and in human kidney stones, the distribution of certain noncollagenous and plasma proteins known to accumulate in bone and other mineralized tissues that include osteopontin, osteocalcin, bone sialoprotein, albumin, and alpha 2HS-glycoprotein. Of these proteins, osteopontin (uropontin) and osteocalcin (or osteocalcin-related gene/protein) were prominent constituents of the calcium oxalate-associated crystal "ghosts" found in the nuclei, lamellae, and striations of the organic matrix of lumenal renal calculi in the rat and of small crystal ghosts found within epithelial cells. Immunocytochemical labeling for both proteins of the content of secretory granules in tubular epithelial cells from treated rats, together with labeling of a similarly textured organic material in the tubular lumen, provides evidence for cosecretion of osteopontin and osteocalcin by epithelial cells, their transit through the urinary filtrate, and ultimately their incorporation into growing renal calculi. In normal rat kidney, osteopontin was localized to the Golgi apparatus of thin loop of Henle cells. In human calcium oxalate monohydrate stones, osteopontin was similarly detected in the lamellae and striations of the organic matrix. Based on these data, it is proposed that during urolithiasis, secretion of osteopontin (uropontin) and osteocalcin (or osteocalcin-related gene/protein), and the subsequent incorporation of these proteins into kidney stone matrix, may influence the nucleation, growth processes, aggregation, and/or tubular adhesion of renal calculi in mammalian kidneys.
长期以来，肾结石的有机基质被认为会影响这些病理性矿物质沉积物中发生的晶体生长。总体而言，在表征矿化组织中的单个有机部分方面取得的最新进展，以及将针对这些分子产生的抗体与不同免疫细胞化学方法结合使用，使得它们在各种正常和病理性矿化组织中的精确分布得以可视化。本超微结构研究报告了使用高分辨率胶体金免疫细胞化学技术在大鼠和人类肾结石中几种非胶原蛋白的上皮表达和细胞外定位。为此，我们在大鼠乙二醇诱导的草酸钙肾结石模型以及人类肾结石中，研究了某些已知在骨骼和其他矿化组织中积累的非胶原蛋白和血浆蛋白的分布，这些蛋白包括骨桥蛋白、骨钙素、骨唾液蛋白、白蛋白和α2HS-糖蛋白。在这些蛋白质中，骨桥蛋白（尿桥蛋白）和骨钙素（或骨钙素相关基因/蛋白）是在大鼠肾盂结石有机基质的细胞核、薄片和条纹中发现的草酸钙相关晶体“幽灵”以及上皮细胞内发现的小晶体幽灵的主要成分。对处理过的大鼠肾小管上皮细胞分泌颗粒内容物中这两种蛋白质的免疫细胞化学标记，以及对肾小管腔中类似质地有机物质的标记，为上皮细胞共分泌骨桥蛋白和骨钙素、它们通过尿液滤液转运以及最终并入生长中的肾结石提供了证据。在正常大鼠肾脏中，骨桥蛋白定位于髓袢细段细胞的高尔基体。在人类一水草酸钙结石中，同样在有机基质的薄片和条纹中检测到骨桥蛋白。基于这些数据，有人提出在肾结石形成过程中，骨桥蛋白（尿桥蛋白）和骨钙素（或骨钙素相关基因/蛋白）的分泌以及随后这些蛋白质并入肾结石基质，可能会影响哺乳动物肾脏中肾结石的成核、生长过程、聚集和/或肾小管黏附。
