Nephronectin expression in nephrotoxic acute tubular necrosis.
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 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.


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.


CONCLUSIONS
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.
Cheng
Chao-Wen
CW
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Ka
Shuk-Man
SM
Yang
Shun-Min
SM
Shui
Hao-Ai
HA
Hung
Yao-Wen
YW
Ho
Pei-Chun
PC
Su
Yung-Chih
YC
Chen
Ann
A
D000818:Animals; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D007683:Kidney Tubular Necrosis, Acute / Q000235:genetics / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000502:physiology; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012038:Regeneration
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C432915:nephronectin