期刊
ATHEROSCLEROSIS
卷 195, 期 2, 页码 303-312出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2007.01.005
关键词
integrin; migration; phenotype; smooth muscle cell; actin stress fibres
Loss of the differentiated (contractile) phenotype of vascular smooth muscle cells (VSMCs) heightens their migratory activity. Integrins, as the main integrators of cell-extracellular matrix, regulate different aspects of cell behavior including migration and differentiation. alpha 8 beta 1 Integrin being expressed in cell types with contractile abilities is downregulated during VSMC phenotype modulation. In this report the ability of alpha 8 beta 1 integrin to induce the characteristics of the contractile phenotype as well as suppression of VSMC migratory activity was investigated. Forced expression of alpha 8 integrin in passage-5 rat VSMCs resulted in lower migratory activity. Western blot and immunoconfocal studies revealed that alpha 8 integrin overexpression was associated with the reappearance of VSMC contractile hallmarks including upregulation of contractile markers, assembly of stress fibres, and increased number of focal adhesions. alpha 8 Integrin overexpression in fibroblast-like Rat1 cells also induced SMC-like characteristics. alpha 8 Integrin-induced reappearance of the contractile hallmarks in de-differentiated VSMCs was impaired by RhoA inhibitors. These results provide evidences that alpha 8 integrin overexpression may assist phenotype-modulated VSMCs to revert to the contractile phenotype possibly via RhoA signaling pathway. Our findings suggest a dynamic role for alpha 8 beta 1 integrin to induce contractile phenotype as well as suppression of VSMC migration, a key player during arterial stenosis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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