Verstrepen W A, Persy V P, Verhulst A, Dauwe S, De Broe M E
Department of Nephrology-Hypertension, University of Antwerp, Belgium.
Nephrol Dial Transplant. 2001 Apr;16(4):712-24. doi: 10.1093/ndt/16.4.712.
The effect of segment-specific proximal tubular injury on spatio-temporal osteopontin (OPN) distribution was determined in two different nephrotoxic rat models to evaluate its conceivability with a possible role for OPN in acute renal failure (ARF). OPN gene expression was further determined in proximal and distal tubular cells to investigate the origin of increased renal OPN.
Renal OPN protein and mRNA expression were compared in the rat during mercuric-chloride- vs gentamicin-induced ARF using immunohistochemistry and in situ hybridization.
Mercuric chloride primarily induced tubular injury and subsequent cell proliferation in proximal straight tubules (PST), whereas gentamicin predominantly injured proximal convoluted tubules (PCT). In both models, the distribution of OPN protein was associated with increased OPN mRNA levels in proximal as well as distal tubular cells. However, upregulation was delayed in the proximal tubular segment suffering most from injury, i.e. PCT in gentamicin ARF vs PST in mercuric-chloride ARF. OPN immunostaining at the apical cell membrane from distal tubules was in contrast to perinuclear vesicular staining in proximal tubular cells.
OPN gene and protein expression is induced in both proximal and distal tubular cells during rat toxic ARF. The distinct subcellular localization in proximal vs distal tubular cells indicates differences in OPN processing and/or handling. The spatio-temporal distribution is consistent with a possible role in renal injury and regeneration.
在两种不同的肾毒性大鼠模型中，确定了节段特异性近端肾小管损伤对时空骨桥蛋白（OPN）分布的影响，以评估其与OPN在急性肾衰竭（ARF）中可能发挥的作用的相关性。进一步测定近端和远端肾小管细胞中的OPN基因表达，以研究肾脏OPN增加的来源。
使用免疫组织化学和原位杂交技术，比较了氯化汞和庆大霉素诱导的ARF大鼠肾脏中OPN蛋白和mRNA的表达。
氯化汞主要诱导近端直小管（PST）的肾小管损伤和随后的细胞增殖，而庆大霉素主要损伤近端曲小管（PCT）。在两种模型中，OPN蛋白的分布与近端和远端肾小管细胞中OPN mRNA水平的增加相关。然而，在受损伤最严重的近端肾小管节段中，上调出现延迟，即在庆大霉素ARF中为PCT，而在氯化汞ARF中为PST。远端小管顶端细胞膜上的OPN免疫染色与近端肾小管细胞中的核周囊泡染色形成对比。
在大鼠中毒性ARF期间，近端和远端肾小管细胞中均诱导了OPN基因和蛋白表达。近端和远端肾小管细胞中不同的亚细胞定位表明OPN加工和/或处理存在差异。时空分布与在肾损伤和再生中的可能作用一致。
