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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2010-7-12
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pubmed:abstractText |
Alport syndrome is a hereditary type IV collagen disease leading to progressive renal fibrosis, hearing loss and ocular changes. End stage renal failure usually develops during adolescence. COL4A3-/- mice serve as an animal model for progressive renal scarring in Alport syndrome. The present study evaluates the role of Discoidin Domain Receptor 1 (DDR1) in cell-matrix interaction involved in pathogenesis of Alport syndrome including renal inflammation and fibrosis. DDR1/COL4A3 Double-knockouts were compared to COL4A3-/- mice with 50% or 100% expression of DDR1, wildtype controls and to DDR1-/- COL4A3+/+ controls for over 6years. Double-knockouts lived 47% longer, mice with 50% DDR1 lived 29% longer and showed improved renal function (reduction in proteinuria and blood urea nitrogen) compared to animals with 100% DDR1 expression. Loss of DDR1 reduced proinflammatory, profibrotic cells via signaling of TGFbeta, CTGF, NFkappaB and IL-6 and decreased deposition of extracellular matrix. Immunogold-staining and in-situ hybridisation identified podocytes as major players in DDR1-mediated fibrosis and inflammation within the kidney. In summary, glomerular epithelial cells (podocytes) express DDR1. Loss of DDR1-expression in the kidney delayed renal fibrosis and inflammation in hereditary type IV collagen disease. This supports our hypothesis that podocyte-matrix interaction via collagen receptors plays an important part in progression of renal fibrosis in Alport disease. The blockade of collagen-receptor DDR1 might serve as an important new therapeutic concept in progressive fibrotic and inflammatory diseases in the future.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type IV,
http://linkedlifedata.com/resource/pubmed/chemical/Connective Tissue Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Ctgf protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ddr1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Urea
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1569-1802
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pubmed:author |
pubmed-author:BeirowskiBogdanB,
pubmed-author:BusseAnn-ChristinAC,
pubmed-author:GirgertRainerR,
pubmed-author:GrossOliverO,
pubmed-author:KangHee GyungHG,
pubmed-author:KretzlerMatthiasM,
pubmed-author:KruegelJennyJ,
pubmed-author:MüllerGerhard-AntonGA,
pubmed-author:MiosgeNicolaiN,
pubmed-author:SegererStephanS,
pubmed-author:VogelWolfgang FWF,
pubmed-author:WeberManfredM
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pubmed:copyrightInfo |
Copyright (c) 2010 Elsevier B.V. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
346-56
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pubmed:meshHeading |
pubmed-meshheading:20307660-Animals,
pubmed-meshheading:20307660-Antigens, CD3,
pubmed-meshheading:20307660-Collagen Type IV,
pubmed-meshheading:20307660-Connective Tissue Growth Factor,
pubmed-meshheading:20307660-Female,
pubmed-meshheading:20307660-Fibrosis,
pubmed-meshheading:20307660-Humans,
pubmed-meshheading:20307660-Immunohistochemistry,
pubmed-meshheading:20307660-In Situ Hybridization,
pubmed-meshheading:20307660-Kidney Glomerulus,
pubmed-meshheading:20307660-Longevity,
pubmed-meshheading:20307660-Male,
pubmed-meshheading:20307660-Mice,
pubmed-meshheading:20307660-Mice, Inbred ICR,
pubmed-meshheading:20307660-Mice, Knockout,
pubmed-meshheading:20307660-Microscopy, Electron,
pubmed-meshheading:20307660-NF-kappa B,
pubmed-meshheading:20307660-Nephritis, Hereditary,
pubmed-meshheading:20307660-Proteinuria,
pubmed-meshheading:20307660-RNA,
pubmed-meshheading:20307660-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:20307660-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20307660-Transforming Growth Factor beta,
pubmed-meshheading:20307660-Urea
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pubmed:year |
2010
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pubmed:articleTitle |
Loss of collagen-receptor DDR1 delays renal fibrosis in hereditary type IV collagen disease.
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pubmed:affiliation |
Department of Nephrology & Rheumatology, University Medicine Goettingen Robert-Koch Strasse 40, Goettingen, Germany. gross.oliver@med.uni-goettingen.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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