| Novel role for STAT-5B in the regulation of Hsp27-FGF-2 axis facilitating thrombin-induced vascular smooth muscle cell growth and motility. | |
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MedLine Citation:
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PMID: 16527988 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previously, we have demonstrated that STAT-3 plays a role in thrombin-induced VSMC motility. To learn more about the role of STATs in the mitogenic and chemotactic signaling events of thrombin, here we have studied the role of STAT-5. Thrombin activated STAT-5 as measured by its tyrosine phosphorylation, DNA binding, and reporter gene activity. Inhibition of STAT-5B, but not STAT-5A, by adenovirus-mediated expression of its respective dominant-negative mutants suppressed thrombin-induced VSMC growth and motility. Thrombin induced the expression of Hsp27 and FGF-2 in a time- and STAT-5B-dependent manner in VSMC. In addition, small interfering RNA-directed depletion of Hsp27 levels or adenovirus-mediated expression of its dominant-negative mutant attenuated thrombin-induced FGF-2 expression, growth, and motility of VSMC. An increased association of STAT-5B with STAT-3 occurred in response to thrombin and adenovirus-mediated expression of dnSTAT-3 suppressed thrombin-induced Hsp27 and FGF-2 induction, DNA synthesis and motility in VSMC. Together, these results indicate that thrombin-induced VSMC growth and motility require STAT-5B/STAT-3-dependent expression of Hsp27 and FGF-2. These observations also suggest that STAT-5B/STAT-3/Hsp27/FGF-2 signaling via its involvement in the regulation of VSMC growth and motility may play an important role in the pathogenesis of vascular diseases such as restenosis after angioplasty. |
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Authors:
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Huiqing Cao; Nagadhara Dronadula; Farhan Rizvi; Quanyi Li; Kalyan Srivastava; William T Gerthoffer; Gadiparthi N Rao |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-03-09 |
Journal Detail:
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Title: Circulation research Volume: 98 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-04-14 Completed Date: 2006-05-03 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 913-22 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Movement DNA Primers Fibroblast Growth Factor 2 / genetics, physiology* HSP27 Heat-Shock Proteins Heat-Shock Proteins / genetics, metabolism* Muscle, Smooth, Vascular / growth & development, physiology* Neoplasm Proteins / genetics, metabolism* Polymerase Chain Reaction Rats STAT3 Transcription Factor / physiology* STAT5 Transcription Factor / genetics, metabolism* Thrombin / physiology* Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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HL64165/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/HSP27 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Hspb1 protein, rat; 0/Neoplasm Proteins; 0/STAT3 Transcription Factor; 0/STAT5 Transcription Factor; 0/Stat3 protein, rat; 0/Stat5b protein, rat; 103107-01-3/Fibroblast Growth Factor 2; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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