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NDT Advance Access published online on November 5, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm496
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Nephronectin expression in nephrotoxic acute tubular necrosis

Chao-Wen Cheng1, Shuk-Man Ka1, Shun-Min Yang2, Hao-Ai Shui3, Yao-Wen Hung4, Pei-Chun Ho1, Yung-Chih Su1 and Ann Chen1

1Department of Pathology, Tri-Service General Hospital, 2Graduate Institute of Life Sciences, 3Graduate Institute of Medical Sciences, and 4Electron Microscopy Unit, Institute of Preventive Medicine, National Defense Medical Center, Taiwan, ROC

Correspondence and offprint requests to: Dr Ann Chen, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Gung Road, Taipei, Taiwan, ROC. Email: doc31717{at}ndmctsgh.edu.tw



  Abstract

Background. 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 {alpha}8ß1 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.

Methods. 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.

Results. 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.

Conclusion. 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.

Keywords: acute tubular necrosis; nephronectin; PCNA; regeneration; urine biomarker

Received for publication: 28.12.06
Accepted in revised form: 29. 6.07


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