Document Detail

Relationship of connexin43 expression to phenotypic modulation in cultured human aortic smooth muscle cells.
MedLine Citation:
PMID:  17651863     Owner:  NLM     Status:  MEDLINE    
Transition of arterial smooth muscle cells from the contractile to the synthetic phenotype in vivo is associated with up-regulation of the gap-junctional protein, connexin43 (Cx43). However, the role of increased Cx43 expression in relation to the characteristic features of the synthetic phenotype - altered growth, differentiation or synthetic activity - has not previously been defined. In the present study, growth was induced in cultured human aortic smooth muscle cells by treatment with thrombin and with PDGF-bb; growth arrest was induced by serum deprivation and contact inhibition. Alterations in Cx43 expression and gap-junctional communication were analyzed in relation to expression of markers for contractile differentiation and extracellular matrix synthesis. Treatment with thrombin, but not PDGF-bb, led to up-regulation of Cx43 gap junctions, increased synthetic activity yet also enhanced contractile differentiation. Inhibition of growth by deprivation of serum growth factors in sub-confluent cultures had no effect on Cx43 expression or contractile differentiation. Growth arrest by contact inhibition led to progressive reduction in Cx43 expression, in parallel with progressive increase in expression of differentiation markers but no alteration in synthetic activity. Of a range of stimuli examined, only thrombin had the combined effect of increasing Cx43 gap-junction communication, growth and synthesis, yet it also enhanced contractile differentiation. Down-regulation of Cx43 and improved contractile differentiation occurred only when growth arrest was induced through the contact-inhibition pathway, though, in this instance, synthesis remained undiminished. We conclude that Cx43 levels, though having common correlates, are not exclusively linked to the cell phenotype or the state of growth.
Tsutomu Matsushita; Aisha Rama; Nicoletta Charolidi; Emmanuel Dupont; Nicholas J Severs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-24
Journal Detail:
Title:  European journal of cell biology     Volume:  86     ISSN:  0171-9335     ISO Abbreviation:  Eur. J. Cell Biol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-24     Completed Date:  2007-11-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906240     Medline TA:  Eur J Cell Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  617-28     Citation Subset:  IM    
Cardiac Medicine, National Heart and Lung Institute (Imperial College London), Guy Scadding Building, Dovehouse Street, London SW3 6LY, UK.
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MeSH Terms
Angiogenesis Inducing Agents / pharmacology
Aorta / cytology*,  metabolism
Blotting, Northern
Blotting, Western
Cell Communication
Cell Differentiation
Cell Proliferation
Cells, Cultured
Connexin 43 / metabolism*
Fluorescent Antibody Technique
Gap Junctions / metabolism
Hemostatics / pharmacology
Muscle Contraction
Muscle, Smooth, Vascular / metabolism*
Platelet-Derived Growth Factor / pharmacology
Thrombin / pharmacology
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Connexin 43; 0/Hemostatics; 0/Platelet-Derived Growth Factor; 0/platelet-derived growth factor BB; EC

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