Transcriptional response in the unaffected kidney after contralateral hydronephrosis or nephrectomy.
BACKGROUND
Unilateral loss of kidney function is followed by compensatory contralateral growth. The early, genome-wide transcriptional response of the untouched kidney to unilateral ureteral obstruction (UUO) or unilateral nephrectomy is unknown.


METHODS
Twelve adult male Sprague-Dawley rats were subjected to UUO and twelve rats to unilateral nephrectomy. At time points 12, 24, and 72 hours after insult four rats each were sacrificed and the contralateral kidney harvested for genome-wide gene expression analysis, transcription factor analysis, and histomorphology.


RESULTS
Microarray studies revealed that the majority of differentially expressed transcripts were suppressed in UUO and unilateral nephrectomy compared to control kidneys. The function of these suppressed genes is predominantly growth inhibition and apoptosis suggesting a net pro-hypertrophic response. Insulin-like growth factor-2 (IGF-2)-binding protein was one of the few activated genes. We observed a distinctly different molecular signature between UUO and unilateral nephrectomy at the three time points investigated. The early response in UUO rats suggests a counterbalance to the nonfiltering kidney by activation of transport pathways such as the aquaporins. Unilateral nephrectomy kidneys, on the other hand, respond immediately to contralateral nephrectomy by activation of cell cycle regulators such as the cyclin family. Several genes with weakly defined function were found to be associated with either UUO or unilateral nephrectomy. Transcription factor analysis of the identified transcripts suggests common regulation at least of some of these genes. All kidneys showed normal histology.


CONCLUSIONS
Release of growth inhibition by nephrectomy leads to immediate cell cycle activation after unilateral nephrectomy, whereas UUO kidneys counterbalance filtration failure by activation of several transporters.
Hauser
Peter
P
Department of Nephrology, Medical University Vienna, Austria.
Kainz
Alexander
A
Perco
Paul
P
Bergmeister
Helga
H
Mitterbauer
Christa
C
Schwarz
Christoph
C
Regele
Heinz M
HM
Mayer
Bernd
B
Meyer
Timothy W
TW
Oberbauer
Rainer
R
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D006869:Hydronephrosis / Q000235:genetics* / Q000503:physiopathology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D007668:Kidney / Q000502:physiology* / Q000601:surgery; D008297:Male; D009392:Nephrectomy; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology*; D014517:Ureteral Obstruction / Q000235:genetics / Q000503:physiopathology
D002352:Carrier Proteins; D014157:Transcription Factors; D007335:Insulin-Like Growth Factor II