rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-1-3
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pubmed:abstractText |
The transforming growth factor (TGF)-beta-inducible integrin alpha v beta6 is preferentially expressed at sites of epithelial remodeling and has been shown to bind and activate latent precursor TGF-beta. Herein, we show that alpha v beta6 is overexpressed in human kidney epithelium in membranous glomerulonephritis, diabetes mellitus, IgA nephropathy, Goodpasture's syndrome, and Alport syndrome renal epithelium. To assess the potential regulatory role of alpha v beta6 in renal disease, we studied the effects of function-blocking alpha v beta6 monoclonal antibodies (mAbs) and genetic ablation of the beta6 subunit on kidney fibrosis in Col4A3-/- mice, a mouse model of Alport syndrome. Expression of alpha v beta6 in Alport mouse kidneys was observed primarily in cortical tubular epithelial cells and in correlation with the progression of fibrosis. Treatment with alpha v beta6-blocking mAbs inhibited accumulation of activated fibroblasts and deposition of interstitial collagen matrix. Similar inhibition of renal fibrosis was observed in beta6-deficient Alport mice. Transcript profiling of kidney tissues showed that alpha v beta6-blocking mAbs significantly inhibited disease-associated changes in expression of fibrotic and inflammatory mediators. Similar patterns of transcript modulation were produced with recombinant soluble TGF-beta RII treatment, suggesting shared regulatory functions of alpha v beta6 and TGF-beta. These findings demonstrate that alpha v beta6 can contribute to the regulation of renal fibrosis and suggest this integrin as a potential therapeutic target.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0002-9440
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pubmed:author |
pubmed-author:AllaireNormand ENE,
pubmed-author:Chun WangLiL,
pubmed-author:DolinskiBrian MBM,
pubmed-author:FogoAgnesA,
pubmed-author:GardnerHumphrey AHA,
pubmed-author:HahmKyungminK,
pubmed-author:HoranGerald SGS,
pubmed-author:ItoRR,
pubmed-author:KalluriRaghuR,
pubmed-author:LeoneDiane RDR,
pubmed-author:LobbRoy RRR,
pubmed-author:LukashevMatvey EME,
pubmed-author:McCrannDonald JDJ,
pubmed-author:SheppardDeanD,
pubmed-author:ShieldCharles FCF3rd,
pubmed-author:SimonKenneth JKJ,
pubmed-author:VioletteShelia MSM,
pubmed-author:WeinrebPaul HPH,
pubmed-author:YangWilliam JWJ
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pubmed:issnType |
Print
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pubmed:volume |
170
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
110-25
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17200187-Animals,
pubmed-meshheading:17200187-Antibodies, Blocking,
pubmed-meshheading:17200187-Antigens, Neoplasm,
pubmed-meshheading:17200187-Disease Models, Animal,
pubmed-meshheading:17200187-Extracellular Matrix,
pubmed-meshheading:17200187-Fibroblasts,
pubmed-meshheading:17200187-Fibrosis,
pubmed-meshheading:17200187-Humans,
pubmed-meshheading:17200187-Immunohistochemistry,
pubmed-meshheading:17200187-Integrins,
pubmed-meshheading:17200187-Kidney,
pubmed-meshheading:17200187-Mice,
pubmed-meshheading:17200187-Mice, Knockout,
pubmed-meshheading:17200187-NIH 3T3 Cells,
pubmed-meshheading:17200187-Nephritis, Hereditary,
pubmed-meshheading:17200187-Transforming Growth Factor beta,
pubmed-meshheading:17200187-Up-Regulation
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pubmed:year |
2007
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pubmed:articleTitle |
Alphav beta6 integrin regulates renal fibrosis and inflammation in Alport mouse.
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pubmed:affiliation |
Department of Exploratory Biology, Biogen Idec, 12 Cambridge Center, Cambridge, MA 02142, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|