Alpha 8 integrin expression is required for maintenance of the smooth muscle cell differentiated phenotype.

Abstract:

OBJECTIVE:Vascular smooth muscle cell (VSMC) de-differentiation is a prerequisite for migration from the tunica media to the intima after vascular injury. Integrin cell adhesion molecules participate in VSMC phenotype modulation. Alpha 8 beta 1 integrin is a differentiation marker of VSMCs and its knockdown heightens migration. In the present study, we examined whether or not alpha 8 integrin is required for the maintenance of VSMC differentiated phenotype. METHODS:Alpha 8 integrin in rat VSMC was knocked down by short interference RNA (siRNA) targeting alpha 8 integrin in comparison to a non-silencing siRNA. Cytoskeletal and morphological changes in VSMC were examined by immunofluorescence staining. The expression of phenotype-dependent markers was analyzed by immunoblotting. RESULTS:Alpha 8 integrin gene silencing evoked drastic changes in characteristics of the VSMC differentiated phenotype, including VSMC morphology, actin fibre organization, focal adhesion assembly and the expression of phenotype-dependent markers in favor of de-differentiation. Then, we investigated whether or not phenotype modulation induced by alpha 8 integrin gene silencing could be reversed by an inducer of VSMC differentiation. Transforming growth factor-beta (TGF-beta) failed to upregulate smooth muscle-myosin heavy chain as well as the assembly of parallel actin fibres in VSMCs transfected by siRNA-alpha 8. In addition, TGF-beta-induced vinculin localization at the tip of the cells was impaired by alpha 8 integrin gene silencing. CONCLUSION:These data suggest that alpha 8 integrin expression is required for maintenance of the VSMC differentiated phenotype, a state that is crucial for non-motile VSMCs.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Zargham R,Thibault G

doi

10.1016/j.cardiores.2006.03.003

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

170-8

issue

1

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(06)00116-7

journal_volume

71

pub_type

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