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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2006-4-17
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pubmed:abstractText |
CCN2 is induced by transforming growth factor-beta (TGFbeta) in fibroblasts and is overexpressed in connective tissue disease. CCN2 has been proposed to be a downstream mediator of TGFbeta action in fibroblasts; however, the role of CCN2 in regulating this process unclear. By using embryonic fibroblasts isolated from ccn2-/- mice, we showed that CCN2 is required for a subset of responses to TGFbeta. Affymetrix genome-wide expression profiling revealed that 942 transcripts were induced by TGFbeta greater than 2-fold in ccn2+/+ fibroblasts, of which 345 were not induced in ccn2-/- fibroblasts, including pro-adhesive and matrix remodeling genes. Whereas TGFbeta properly induced a generic Smad3-responsive promoter in ccn2-/- fibroblasts, TGFbeta-induced activation of focal adhesion kinase (FAK) and Akt was reduced in ccn2-/- fibroblasts. Emphasizing the importance of FAK and Akt activation in CCN2-dependent transcriptional responses to TGFbeta in fibroblasts, CCN2-dependent transcripts were not induced by TGFbeta in fak-/- fibroblasts and were reduced by wortmannin in wild-type fibroblasts. Akt1 overexpression in ccn2-/- fibroblasts rescued the TGFbeta-induced transcription of CCN2-dependent mRNA. Finally, induction of TGFbeta-induced fibroblast adhesion to fibronectin and type I collagen was significantly diminished in ccn2-/- fibroblasts. Thus in embryonic fibroblasts, CCN2 is a necessary cofactor required for TGFbeta to activate the adhesive FAK/Akt/phosphatidylinositol 3-kinase cascade, FAK/Akt-dependent genes, and adhesion to matrix.
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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/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
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/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:AbrahamDavid JDJ,
pubmed-author:BeierFrankF,
pubmed-author:BlackCarol MCM,
pubmed-author:Bou-GhariosGeorgeG,
pubmed-author:CarterDavid EDE,
pubmed-author:ChenYunliangY,
pubmed-author:HowatSarah LSL,
pubmed-author:KennedyLauraL,
pubmed-author:LeaskAndrewA,
pubmed-author:LyonsKaren MKM,
pubmed-author:PalaDaphneD,
pubmed-author:PearsonJeremy DJD,
pubmed-author:RenzoniElisabetta AEA,
pubmed-author:Shi-wenXuX,
pubmed-author:StantonLee AnneLA,
pubmed-author:StrattonRichard JRJ
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10715-26
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16484225-Androstadienes,
pubmed-meshheading:16484225-Animals,
pubmed-meshheading:16484225-Blotting, Western,
pubmed-meshheading:16484225-Cell Adhesion,
pubmed-meshheading:16484225-Collagen,
pubmed-meshheading:16484225-Connective Tissue Growth Factor,
pubmed-meshheading:16484225-Enzyme Inhibitors,
pubmed-meshheading:16484225-Fibroblasts,
pubmed-meshheading:16484225-Fibronectins,
pubmed-meshheading:16484225-Immediate-Early Proteins,
pubmed-meshheading:16484225-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:16484225-Mice,
pubmed-meshheading:16484225-Mice, Transgenic,
pubmed-meshheading:16484225-Nucleic Acid Hybridization,
pubmed-meshheading:16484225-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:16484225-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:16484225-Phosphorylation,
pubmed-meshheading:16484225-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16484225-RNA,
pubmed-meshheading:16484225-RNA, Messenger,
pubmed-meshheading:16484225-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16484225-Signal Transduction,
pubmed-meshheading:16484225-Time Factors,
pubmed-meshheading:16484225-Transcription, Genetic,
pubmed-meshheading:16484225-Transfection,
pubmed-meshheading:16484225-Transforming Growth Factor beta,
pubmed-meshheading:16484225-Transforming Growth Factor beta1
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pubmed:year |
2006
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pubmed:articleTitle |
CCN2 is necessary for adhesive responses to transforming growth factor-beta1 in embryonic fibroblasts.
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pubmed:affiliation |
Centre for Rheumatology, Department of Medicine, University College London (Royal Free Campus), London NW3 2PF, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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