Source:http://linkedlifedata.com/resource/pubmed/id/19643931
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2009-10-1
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pubmed:abstractText |
The accumulation of extracellular matrix proteins is a common feature of fibrotic kidney diseases. Accumulating evidence suggests that TGF-beta and plasminogen activator inhibitor type 1 (PAI-1) promote the development of renal fibrosis by stimulating the generation and inhibiting the removal of matrix proteins. The small heterodimer partner (SHP) represses PAI-1 expression in the liver by inhibiting TGF-beta signaling, but whether SHP inhibits renal fibrosis is unknown. Here, unilateral ureteral obstruction (UUO) markedly increased the expression of PAI-1, type I collagen, and fibronectin but decreased SHP gene expression. Moreover, in kidneys of SHP-/- mice, the expression of PAI-1, type I collagen, fibronectin and alpha-smooth muscle actin (alpha-SMA) were higher compared with those in kidneys of wild-type mice. In addition, loss of SHP accelerated renal fibrosis after UUO. Adenovirus-mediated overexpression of SHP in cultured rat mesangial cells and renal tubular epithelial cells inhibited TGF-beta-stimulated expression of PAI-1, type I collagen, and fibronectin. SHP inhibited TGF-beta- and Smad3-stimulated PAI-1 promoter activities as well as TGF-beta-stimulated binding of Smad3 to its consensus response element on the PAI-1 promoter. Similarly, in vivo, adenovirus-mediated overexpression of SHP in the kidney inhibited the expression of UUO-induced PAI-1, type I collagen, fibronectin, and alpha-SMA. In summary, SHP attenuates renal fibrosis in obstructive nephropathy, making its pathway a possible therapeutic target for chronic kidney disease.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Madh3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/nuclear receptor subfamily 0...,
http://linkedlifedata.com/resource/pubmed/chemical/smooth muscle actin, rat
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1533-3450
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2162-70
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pubmed:dateRevised |
2010-10-4
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pubmed:meshHeading |
pubmed-meshheading:19643931-Actins,
pubmed-meshheading:19643931-Animals,
pubmed-meshheading:19643931-Collagen Type I,
pubmed-meshheading:19643931-Fibronectins,
pubmed-meshheading:19643931-Fibrosis,
pubmed-meshheading:19643931-Kidney,
pubmed-meshheading:19643931-Male,
pubmed-meshheading:19643931-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:19643931-Promoter Regions, Genetic,
pubmed-meshheading:19643931-Rats,
pubmed-meshheading:19643931-Rats, Sprague-Dawley,
pubmed-meshheading:19643931-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:19643931-Smad3 Protein,
pubmed-meshheading:19643931-Transforming Growth Factor beta,
pubmed-meshheading:19643931-Ureteral Obstruction
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pubmed:year |
2009
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pubmed:articleTitle |
The orphan nuclear receptor SHP attenuates renal fibrosis.
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pubmed:affiliation |
Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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