cDNA microarray analysis of adaptive changes after renal ablation in a sclerosis-resistant mouse strain.
BACKGROUND
5/6 nephrectomy (Nx) in susceptible animals causes glomerular sclerosis and interstitial fibrosis in the remnant kidney. Oxidative stress, transforming growth factor-beta (TGF-beta), and the de novo synthesis of collagen seem to contribute to this process. However, these factors might also be required for tissue repair without fibrosis.


METHODS
We examined dynamic changes after nephron loss in a mouse strain capable of complete recovery. C57BL/6 mice underwent single-session Nx and were followed for 40 weeks. Gene expression was monitored over 20 days using 22,000 cDNA microarrays.


RESULTS
The mice developed transient hypertension and glomerular hypertrophy after Nx but failed to progress to glomerular sclerosis or renal failure. Gene expression profiles revealed three stages of recovery, an early phase of injury response, an intermediate phase of extracellular matrix (ECM) production and a later phase of reconstitution. Surprisingly, oxidative stress responses and collagen production were strongly upregulated soon after Nx. Furthermore, TGF-beta(1) and connective tissue growth factor were rapidly upregulated and remained elevated.


CONCLUSIONS
We suggest that oxidative stress, collagen production, profibrotic growth factors and ECM turnover are part of the comprehensive adaptation to nephron loss and not necessarily associated with progressive loss of renal function.
Rumberger
Brigitta
B
Renal Division, Department of Medicine, University Hospital Freiburg, Freiburg, Germany.
Vonend
Oliver
O
Kreutz
Clemens
C
Wilpert
Jochen
J
Donauer
Johannes
J
Amann
Kerstin
K
Rohrbach
Rolf
R
Timmer
Jens
J
Walz
Gerd
G
Gerke
Peter
P
D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005921:Glomerulonephritis / Q000235:genetics* / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D008297:Male; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D003094:Collagen; D045726:Metalloproteases