Nephronectin expression in nephrotoxic acute tubular necrosis

Chao Wen Cheng, Shuk Man Ka, Shun Min Yang, Hao Ai Shui, Yao Wen Hung, Pei Chun Ho, Yung Chih Su, Ann Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 α8β1 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.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalNephrology Dialysis Transplantation
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 2008
Externally publishedYes

Fingerprint

Necrosis
Epithelium
Urine
Oligonucleotide Array Sequence Analysis
Kidney
Regeneration
Immunohistochemistry
Maintenance
nephronectin
Immunoelectron Microscopy
Proliferating Cell Nuclear Antigen
Microarray Analysis
Nuclear Proteins
Morphogenesis
Immunoassay
Acute Kidney Injury
Integrins
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Theoretical Models

Keywords

  • Acute tubular necrosis
  • Nephronectin
  • PCNA
  • Regeneration
  • Urine biomarker

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Cheng, C. W., Ka, S. M., Yang, S. M., Shui, H. A., Hung, Y. W., Ho, P. C., ... Chen, A. (2008). Nephronectin expression in nephrotoxic acute tubular necrosis. Nephrology Dialysis Transplantation, 23(1), 101-109. https://doi.org/10.1093/ndt/gfm496

Nephronectin expression in nephrotoxic acute tubular necrosis. / Cheng, Chao Wen; Ka, Shuk Man; Yang, Shun Min; Shui, Hao Ai; Hung, Yao Wen; Ho, Pei Chun; Su, Yung Chih; Chen, Ann.

In: Nephrology Dialysis Transplantation, Vol. 23, No. 1, 01.2008, p. 101-109.

Research output: Contribution to journalArticle

Cheng, CW, Ka, SM, Yang, SM, Shui, HA, Hung, YW, Ho, PC, Su, YC & Chen, A 2008, 'Nephronectin expression in nephrotoxic acute tubular necrosis', Nephrology Dialysis Transplantation, vol. 23, no. 1, pp. 101-109. https://doi.org/10.1093/ndt/gfm496
Cheng, Chao Wen ; Ka, Shuk Man ; Yang, Shun Min ; Shui, Hao Ai ; Hung, Yao Wen ; Ho, Pei Chun ; Su, Yung Chih ; Chen, Ann. / Nephronectin expression in nephrotoxic acute tubular necrosis. In: Nephrology Dialysis Transplantation. 2008 ; Vol. 23, No. 1. pp. 101-109.
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AB - 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 α8β1 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.

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