DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): modulation during epithelial-mesenchymal transition

Kidney Int. 2003 Dec;64(6):2079-91. doi: 10.1046/j.1523-1755.2003.00306.x.


Background: Tubulointerstitial inflammation and fibrosis are pathologic hallmarks of end-stage renal disease (ESRD). Here we have used DNA microarray technology to monitor the transcriptomic responses to murine unilateral ureteral obstruction (UUO) with a view to identifying molecular modulators of tubulointerstitial fibrosis.

Methods: Using Affymetrix Mu74Av2 microarrays, gene expression 4 and 10 days postobstruction was investigated relative to control contralateral kidneys. Candidate profibrogenic genes were further investigated in epithelial cells undergoing epithelial to mesenchymal transition (EMT) in vitro.

Results: mRNA levels for 1091 gene/EST sequences, of a total of 12,488 displayed on the microarray, were altered twofold or greater by days 4 and 10 postobstruction compared to contralateral control kidneys. Genes were categorised into functional groups, including modulators of cytoskeletal and extracellular matrix metabolism, cell growth, signalling, and transcription/translational events. Among the potentially profibrogenic genes, whose mRNA levels were increased after UUO, were fibroblast-inducible secreted protein (fisp-12), the murine homologue of connective tissue growth factor (CTGF), collagen XVIIIalpha1, secreted protein acidic and rich in cysteine (SPARC), and src-suppressed C-kinase substrate (SSeCKS). A sustained increase in fisp-12 mRNA level was observed during EMT induced by transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF).

Conclusion: Altered gene expression in murine UUO has been demonstrated. Increased expression of fisp-12, SPARC, and SSeCKS has been shown in response to TGF-beta1 treatment and during EMT, suggesting that these genes may offer potential therapeutic targets against tubulointerstitial fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins
  • Animals
  • Cell Cycle Proteins / genetics
  • Cells, Cultured
  • Collagen Type XVIII / genetics
  • Connective Tissue Growth Factor
  • Disease Progression
  • Epidermal Growth Factor / pharmacology
  • Gene Expression
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mitogens / genetics
  • Oligonucleotide Array Sequence Analysis*
  • Osteonectin / genetics
  • Protein Isoforms / genetics
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Ureteral Obstruction / genetics
  • Ureteral Obstruction / metabolism*
  • Ureteral Obstruction / pathology
  • Ureteral Obstruction / physiopathology


  • A Kinase Anchor Proteins
  • Akap12 protein, mouse
  • CCN2 protein, mouse
  • Cell Cycle Proteins
  • Collagen Type XVIII
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Mitogens
  • Osteonectin
  • Protein Isoforms
  • RNA, Messenger
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Connective Tissue Growth Factor
  • Epidermal Growth Factor