title: alpha 8 Integrin overexpression in de-differentiated vascular smooth muscle cells attenuates migratory activity and restores the characteristics of the differentiated phenotype.
abstract: 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.
authors.affiliation: Institut de recherches cliniques de Montréal, Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Ramin
authors.initials: R
authors.lastname: Zargham
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
authors.forename: Gaétan
authors.initials: G
authors.lastname: Thibault
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D039001:Integrin alpha Chains / Q000378:metabolism*; D018613:Microscopy, Confocal; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D015398:Signal Transduction; D015854:Up-Regulation; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D000199:Actins; D039001:Integrin alpha Chains; C093856:integrin alpha8; D020742:rhoA GTP-Binding Protein