Moll S, Menoud P A, French L, Sappino A P, Pastore Y, Schifferli J A, Izui S
Department of Internal Medicine, University of Geneva Medical School, Switzerland.
Am J Pathol. 1998 Apr;152(4):953-62.
Clusterin, a widely distributed glycoprotein, is detected in most tissues and in numerous physiological fluids. In the kidney, this protein is constitutively expressed in tubular epithelial cells, and its expression is enhanced following tubular injuries. In addition, clusterin has been detected in glomerular immune deposits of glomerulonephritis. The present study was designed to define the sites of clusterin mRNA accumulation in murine lupus-like nephritis in comparison with murine tubulopathies. In lupus-like nephritis, a significant increase of clusterin mRNA abundance was demonstrated. This up-regulation was localized exclusively in tubular epithelial cells exhibiting tubulointerstitial alterations, whereas no clusterin mRNA was detectable in diseased glomeruli, excluding an active synthesis of clusterin by glomerular cells. A similar tubular increase of clusterin mRNA abundance was observed in myeloma-like cast nephropathy induced by IgG3 monoclonal cryoglobulins and even in the absence of any detectable histological alterations in a model of septic shock induced by the injection of bacterial lipopolysaccharides. Our results suggest that tubular epithelial cells are the only sites of clusterin mRNA accumulation during the course of lupus-like nephritis and that the tubular up-regulation of clusterin gene expression may reflect the cellular response to various types of tubular injuries.
簇集素是一种广泛分布的糖蛋白，在大多数组织和多种生理液中均可检测到。在肾脏中，这种蛋白在肾小管上皮细胞中组成性表达，且在肾小管损伤后其表达会增强。此外，在肾小球肾炎的肾小球免疫沉积物中也检测到了簇集素。本研究旨在确定与小鼠肾小管疾病相比，簇集素mRNA在小鼠狼疮样肾炎中的积累部位。在狼疮样肾炎中，簇集素mRNA丰度显著增加。这种上调仅局限于表现出肾小管间质改变的肾小管上皮细胞，而在患病的肾小球中未检测到簇集素mRNA，排除了肾小球细胞对簇集素的活跃合成。在由IgG3单克隆冷球蛋白诱导的骨髓瘤样管型肾病中，甚至在注射细菌脂多糖诱导的脓毒症休克模型中，尽管没有任何可检测到的组织学改变，也观察到了簇集素mRNA丰度类似的肾小管增加。我们的结果表明，在狼疮样肾炎病程中，肾小管上皮细胞是簇集素mRNA积累的唯一部位，并且簇集素基因表达的肾小管上调可能反映了细胞对各种类型肾小管损伤的反应。
