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- Title
DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): modulation during epithelial-mesenchymal transition.
- Authors
Higgins, Debra F.; Lappin, David W.P.; Kieran, Niamh E.; Anders, Hans J.; Watson, Ronald W.G.; Strutz, Frank; Schlondorff, Detlef; Haase, Volker H.; Fitzpatrick, John M.; Godson, Catherine; Brady, Hugh R.
- Abstract
DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): Modulation during epithelial-mesenchymal transition. 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 XVIIIα1, 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-β1 (TGF-β1) 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-β1 treatment and during EMT, suggesting that these genes may offer potential therapeutic targets against tubulointerstitial fibrosis.
- Subjects
DNA microarrays; URETERIC obstruction; KIDNEY diseases; RATS; PROTEIN metabolism; RNA metabolism; ANIMAL experimentation; CELL culture; CELL physiology; COLLAGEN; COMPARATIVE studies; EPIDERMAL growth factor; GENE expression; GLYCOPROTEINS; GROWTH factors; RESEARCH methodology; MEDICAL cooperation; MICE; PROTEINS; RESEARCH; RESEARCH funding; EVALUATION research; DISEASE progression; CONNECTIVE tissue growth factor; OLIGONUCLEOTIDE arrays; CELL cycle proteins
- Publication
Kidney International, 2003, Vol 64, Issue 6, p2079
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1046/j.1523-1755.2003.00306.x