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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2007-3-23
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pubmed:abstractText |
The importance of transforming growth factor-beta1 (TGF-beta1) in plasminogen activator inhibitor-1 (PAI-1) gene expression has been established, but the precise intracellular mechanisms are not fully understood. Our hypothesis is that the actin cytoskeleton is involved in TGF-beta1/MAPK-mediated PAI-1 expression in human mesangial cells. Examination of the distributions of actin filaments (F-actin), alpha-actinin, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) by immunofluorescence and immunoprecipitation revealed that ERK and JNK associate with alpha-actinin along F-actin and that TGF-beta1 stimulation promote the dissociation of ERK and JNK with F-actin. Disassembly of the actin cytoskeleton inhibited phosphorylation of ERK and JNK and modulated PAI-1 expression and promoter activity under both basal and TGF-beta1-stimulated conditions. Stabilizing actin prevented dephosphorylation of ERK and JNK. ERK and JNK inhibitors and overexpressed dominant negative mutants antagonized the ability of TGF-beta1 to increase PAI-1 expression and promoter activity. Disassembly of F-actin also inhibited AP-1 DNA binding activity as determined by electrophoretic mobility shift assay using AP-1 consensus oligonucleotides derived from human PAI-1 promoter. F-actin stabilization prevented loss of AP-1 DNA binding activity. Therefore, changes in actin cytoskeleton modulate the ability of TGF-beta1 to stimulate PAI-1 expression through a mechanism dependent on the activation of MAPK/AP-1 pathways.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17328891-10203363,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17328891-10401575,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17328891-9865691
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0014-4827
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
313
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1240-50
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17328891-Actins,
pubmed-meshheading:17328891-Cell Line,
pubmed-meshheading:17328891-Cytoskeleton,
pubmed-meshheading:17328891-Enzyme Activation,
pubmed-meshheading:17328891-Gene Expression Regulation,
pubmed-meshheading:17328891-Humans,
pubmed-meshheading:17328891-Mesangial Cells,
pubmed-meshheading:17328891-Mitogen-Activated Protein Kinases,
pubmed-meshheading:17328891-Models, Biological,
pubmed-meshheading:17328891-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:17328891-Signal Transduction,
pubmed-meshheading:17328891-Smad Proteins,
pubmed-meshheading:17328891-Transforming Growth Factor beta1
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pubmed:year |
2007
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pubmed:articleTitle |
Regulation of TGF-beta1/MAPK-mediated PAI-1 gene expression by the actin cytoskeleton in human mesangial cells.
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pubmed:affiliation |
Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23501, USA. chenyang@mcw.edu
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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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