cDNA microarray analysis of adaptive changes after renal ablation in a sclerosis-resistant mouse strain

Kidney Blood Press Res. 2007;30(6):377-87. doi: 10.1159/000108624. Epub 2007 Sep 20.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / genetics
  • Collagen / metabolism
  • Connective Tissue Growth Factor
  • Extracellular Matrix / metabolism
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Gene Expression Profiling
  • Genetic Predisposition to Disease / genetics*
  • Glomerulonephritis / genetics*
  • Glomerulonephritis / metabolism
  • Hypertension / metabolism
  • Hypertension / pathology
  • Hypertrophy
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / surgery*
  • Male
  • Metalloproteases / genetics
  • Metalloproteases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nephrectomy*
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress / physiology
  • Proteinuria / metabolism
  • Proteinuria / pathology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism


  • CCN2 protein, mouse
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Transforming Growth Factor beta1
  • Connective Tissue Growth Factor
  • Collagen
  • Metalloproteases