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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2011-8-26
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pubmed:abstractText |
Transforming growth factor ? (TGF-?) plays a critical role in tissue fibrosis. The duration and intensity of TGF-? signaling are tightly regulated. Here we report that TSC-22 (TGF-?-stimulated clone 22) facilitates TGF-? signaling by antagonizing Smad7 activity to increase receptor stability. TSC-22 enhances TGF-?-induced Smad2/3 phosphorylation and transcriptional responsiveness. The stimulatory effect of TSC-22 is dependent on Smad7, as silencing Smad7 expression abolishes it. TSC-22 interacts with TGF-? type I receptor T?RI and Smad7 in mutually exclusive ways and disrupts the association of Smad7/Smurfs with T?RI, thereby preventing ubiquitination and degradation of the receptor. We also found that TSC-22 can promote the differentiation of cardiac myofibroblasts by increasing expression of the fibrotic genes for ?-smooth muscle actin (?-SMA), PAI-1, fibronectin, and collagen I, which is consistent with upregulation of TSC-22, phospho-Smad2/3, and the fibrotic genes in isoproterenol-induced rat myocardial fibrotic hearts. Taken together with the notion that TGF-? induces TSC-22 expression, our findings suggest that TSC-22 regulates TGF-? signaling via a positive-feedback mechanism and may contribute to myocardial fibrosis.
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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 |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Madh2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Madh3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Smurf1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1i4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1098-5549
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3700-9
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pubmed:meshHeading |
pubmed-meshheading:21791611-Animals,
pubmed-meshheading:21791611-Cell Differentiation,
pubmed-meshheading:21791611-Fibrosis,
pubmed-meshheading:21791611-Fluorescent Antibody Technique,
pubmed-meshheading:21791611-HEK293 Cells,
pubmed-meshheading:21791611-Humans,
pubmed-meshheading:21791611-Immunoblotting,
pubmed-meshheading:21791611-Immunoprecipitation,
pubmed-meshheading:21791611-Mice,
pubmed-meshheading:21791611-Myocardium,
pubmed-meshheading:21791611-Myofibroblasts,
pubmed-meshheading:21791611-Phosphorylation,
pubmed-meshheading:21791611-Protein-Serine-Threonine Kinases,
pubmed-meshheading:21791611-RNA, Small Interfering,
pubmed-meshheading:21791611-RNA Interference,
pubmed-meshheading:21791611-Rats,
pubmed-meshheading:21791611-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:21791611-Repressor Proteins,
pubmed-meshheading:21791611-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21791611-Signal Transduction,
pubmed-meshheading:21791611-Smad2 Protein,
pubmed-meshheading:21791611-Smad3 Protein,
pubmed-meshheading:21791611-Smad7 Protein,
pubmed-meshheading:21791611-Transforming Growth Factor beta,
pubmed-meshheading:21791611-Ubiquitin-Protein Ligases,
pubmed-meshheading:21791611-Ubiquitination
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pubmed:year |
2011
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pubmed:articleTitle |
TSC-22 promotes transforming growth factor ?-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity.
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pubmed:affiliation |
The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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