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

DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): Modulation during epithelial-mesenchymal transition. Tubulointerstitial inflammation and fibrosis are pathologic hallmarks of end-stage renal di...

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Veröffentlicht in:Kidney international 2003-12, Vol.64 (6), p.2079-2091
Hauptverfasser: 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.
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container_end_page 2091
container_issue 6
container_start_page 2079
container_title Kidney international
container_volume 64
creator 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.
description DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): Modulation during epithelial-mesenchymal transition. 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. Using Affymetrix Mu74Av2 microarrays, gene expression 4 and 10days 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. 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). 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.
doi_str_mv 10.1046/j.1523-1755.2003.00306.x
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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. Using Affymetrix Mu74Av2 microarrays, gene expression 4 and 10days 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. 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. 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Renal failure ; Oligonucleotide Array Sequence Analysis ; Osteonectin - genetics ; profibrogenic genes ; Protein Isoforms - genetics ; renal fibrosis ; RNA, Messenger - metabolism ; SPARC ; SSeCKS ; Transforming Growth Factor beta - pharmacology ; Transforming Growth Factor beta1 ; Ureteral Obstruction - genetics ; Ureteral Obstruction - metabolism ; Ureteral Obstruction - pathology ; Ureteral Obstruction - physiopathology ; UUO</subject><ispartof>Kidney international, 2003-12, Vol.64 (6), p.2079-2091</ispartof><rights>2003 International Society of Nephrology</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c606t-1808a5e404a72f781dedc2843a2f29e4a8a3e90c693cb082f20b51578b1a6d013</citedby><cites>FETCH-LOGICAL-c606t-1808a5e404a72f781dedc2843a2f29e4a8a3e90c693cb082f20b51578b1a6d013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=15288796$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14633130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Higgins, Debra F.</creatorcontrib><creatorcontrib>Lappin, David W.P.</creatorcontrib><creatorcontrib>Kieran, Niamh E.</creatorcontrib><creatorcontrib>Anders, Hans J.</creatorcontrib><creatorcontrib>Watson, Ronald W.G.</creatorcontrib><creatorcontrib>Strutz, Frank</creatorcontrib><creatorcontrib>Schlondorff, Detlef</creatorcontrib><creatorcontrib>Haase, Volker H.</creatorcontrib><creatorcontrib>Fitzpatrick, John M.</creatorcontrib><creatorcontrib>Godson, Catherine</creatorcontrib><creatorcontrib>Brady, Hugh R.</creatorcontrib><title>DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): Modulation during epithelial-mesenchymal transition</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): Modulation during epithelial-mesenchymal transition. 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. Using Affymetrix Mu74Av2 microarrays, gene expression 4 and 10days 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. 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. 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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. Using Affymetrix Mu74Av2 microarrays, gene expression 4 and 10days 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. 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). 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.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>14633130</pmid><doi>10.1046/j.1523-1755.2003.00306.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
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subjects A Kinase Anchor Proteins
Animals
Biological and medical sciences
Cell Cycle Proteins - genetics
Cells, Cultured
Collagen Type XVIII - genetics
collagen XVIIIα1
Connective Tissue Growth Factor
Disease Progression
Epidermal Growth Factor - pharmacology
fisp-12
Gene Expression
Immediate-Early Proteins - genetics
Immediate-Early Proteins - metabolism
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Interstitial nephritis
Medical sciences
Mice
Mice, Inbred C57BL
microarray analysis
Mitogens - genetics
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Oligonucleotide Array Sequence Analysis
Osteonectin - genetics
profibrogenic genes
Protein Isoforms - genetics
renal fibrosis
RNA, Messenger - metabolism
SPARC
SSeCKS
Transforming Growth Factor beta - pharmacology
Transforming Growth Factor beta1
Ureteral Obstruction - genetics
Ureteral Obstruction - metabolism
Ureteral Obstruction - pathology
Ureteral Obstruction - physiopathology
UUO
title DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): Modulation during epithelial-mesenchymal transition
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