title: Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway.
abstract: Smooth muscle cell (SMC) migration involves interactions of integrin receptors with extracellular matrix (ECM) and is an important process of neointimal formation in atherosclerosis and restenosis after vascular interventions. Previous studies have shown that periostin (PN), a novel ECM protein, is upregulated in rat carotid artery after balloon injury, and growth factor-stimulated expression of PN promotes SMC migration in vitro. Here, we address the mechanism by which PN-integrin interaction mediates SMC migration in vitro. Aortic SMCs isolated from PN null mice exhibited a significantly reduced ability to migrate and proliferate in vitro. Endogenous PN protein was absent and very low in the culture medium from the primary cultures of PN-/- and wildtype SMCs, respectively. In both types of SMCs, adenovirus-mediated overexpression of HA-tagged PN to a similar extent, which induced a robust cell migration concomitantly with an increase in beta3-integrin expression and phosphorylation of FAK (Tyr397). Furthermore, in cultured human SMCs, specific integrin blocking antibodies showed that interactions of PN-alphanubeta3 and PN-alphanubeta5, but not PN-beta1 integrins, are required for SMC migration. Inhibition of FAK signaling by overexpression of an endogenous FAK inhibitor termed FRNK (FAK-related nonkinase) significantly attenuated FAK (Tyr397) phosphorylation and the SMC migration induced by PN. These results reveal a mechanism whereby PN mediates vascular SMC migration through an interaction with alphaV-integrins (mainly alphanubeta3) and subsequent activation of FAK pathway.
authors.affiliation: Department of Neurosurgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, United States. gli@lsuhsc.edu
authors.forename: Guohong
authors.initials: G
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Jin
authors.forename: Russell A
authors.initials: RA
authors.lastname: Norris
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Shiyong
authors.initials: S
authors.lastname: Yu
authors.forename: Fusheng
authors.initials: F
authors.lastname: Wu
authors.forename: Roger R
authors.initials: RR
authors.lastname: Markwald
authors.forename: Anil
authors.initials: A
authors.lastname: Nanda
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Susan S
authors.initials: SS
authors.lastname: Smyth
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D005434:Flow Cytometry / Q000379:methods; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D039302:Integrin alphaVbeta3; C512835:POSTN protein, human; C082838:Postn protein, mouse; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D051416:Focal Adhesion Protein-Tyrosine Kinases
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