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Relationship of connexin43 expression to phenotypic modulation in cultured human aortic smooth muscle cells

Matsushita, T, Rama, A, Charolidi, N, Dupont, E and Severs, NJ (2007) Relationship of connexin43 expression to phenotypic modulation in cultured human aortic smooth muscle cells EUR J CELL BIOL, 86 (10). pp. 617-628.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
Matsushita, T
Rama, A
Charolidi, N
Dupont, E
Severs, NJ
Date : October 2007
DOI : 10.1016/j.ejcb.2007.06.005
Uncontrolled Keywords : gap junctions, connexins, cell-to-cell communication, vascular smooth muscle cells, phenotypic transition, FIBROBLAST-GROWTH-FACTOR, GAP-JUNCTIONS, UP-REGULATION, INTERCELLULAR COMMUNICATION, IN-VIVO, DISEASE, HEART, ATHEROSCLEROSIS, DIFFERENTIATION, PROTEINS
Additional Information : NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Cell Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in European Journal of Cell Biology, 86(10), October 2007, DOI 10.1016/j.ejcb.2007.06.005
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 14:39
Last Modified : 31 Oct 2017 14:25

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