Cheng Chao-Wen, Ka Shuk-Man, Yang Shun-Min, Shui Hao-Ai, Hung Yao-Wen, Ho Pei-Chun, Su Yung-Chih, Chen Ann
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Nephrol Dial Transplant. 2008 Jan;23(1):101-9. doi: 10.1093/ndt/gfm496. Epub 2007 Nov 5.
Acute tubular necrosis (ATN) is characterized by an initiation phase, followed by an extension phase, and a maintenance and recovery phase, the latter of which involves increased regeneration of tubular cells. Nephronectin (NPNT), a ligand for alpha8beta1 integrin, is expressed in the ureteric bud epithelium during kidney morphogenesis. However, little is known about the potential involvement of NPNT in the regeneration phase of ATN.
cDNA microarray, real-time polymerase chain reaction, in situ hybridization, immunohistochemistry, immuno-electron microscopy and immunoassay (for urine) were used to identify the time-course NPNT expression in a murine model of ATN.
The gene transcript of NPNT was examined during a 14-day course of ATN by a cursory cDNA microarray analysis. Although NPNT was observed focally in normal renal tubular epithelium, it was greatly expressed in regenerating tubular cells during the maintenance and recovery phases of ATN. As early as day 1 following onset of ATN, NPNT was already present in the urine. Importantly, NPNT expression preceded proliferating cell nuclear antigen protein expression in regenerating renal tubular epithelial cells, as demonstrated by double immunohistochemistry.
The present study was the first to identify an enhanced expression of NPNT in regenerating tubular epithelium in an experimental model of ATN. NPNT may play a crucial role in the regenerating process of nephrotoxic ATN. Our data also suggest that NPNT may provide a useful tissue and urine biomarker for both the development and evolution of nephrotoxic acute renal injury.
急性肾小管坏死（ATN）的特点是起始期，随后是扩展期，以及维持和恢复期，后者涉及肾小管细胞再生增加。肾连蛋白（NPNT）是α8β1整合素的配体，在肾脏形态发生过程中在输尿管芽上皮中表达。然而，关于NPNT在ATN再生期的潜在作用知之甚少。
采用cDNA微阵列、实时聚合酶链反应、原位杂交、免疫组织化学、免疫电子显微镜和免疫测定（用于尿液）来确定ATN小鼠模型中NPNT表达的时间进程。
通过粗略的cDNA微阵列分析在14天的ATN病程中检测NPNT的基因转录本。虽然在正常肾小管上皮中局部观察到NPNT，但在ATN的维持和恢复期，它在再生的肾小管细胞中大量表达。早在ATN发病后第1天，NPNT就已出现在尿液中。重要的是，双重免疫组织化学表明，NPNT表达先于再生肾小管上皮细胞中增殖细胞核抗原蛋白的表达。
本研究首次在ATN实验模型中发现再生肾小管上皮中NPNT表达增强。NPNT可能在肾毒性ATN的再生过程中起关键作用。我们的数据还表明，NPNT可能为肾毒性急性肾损伤的发生和发展提供有用的组织和尿液生物标志物。
