Periostin mediates vascular smooth muscle cell migration through the integrins ανβ3 and ανβ5 and focal adhesion kinase (FAK) pathway

Guohong Li, Rong Jin, Russell A. Norris, Lin Zhang, Shiyong Yu, Fusheng Wu, Roger R. Markwald, Anil Nanda, Simon J. Conway, Susan S. Smyth, D. Neil Granger

Research output: Contribution to journalArticle

97 Scopus citations

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 β3-integrin expression and phosphorylation of FAK (Tyr397). Furthermore, in cultured human SMCs, specific integrin blocking antibodies showed that interactions of PN-ανβ3 and PN-ανβ5, but not PN-β1 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 ανβ3) and subsequent activation of FAK pathway.

Original languageEnglish (US)
Pages (from-to)358-365
Number of pages8
JournalAtherosclerosis
Volume208
Issue number2
DOIs
StatePublished - Feb 1 2010

Keywords

  • FAK
  • FRNK
  • Integrin receptors
  • Migration
  • Periostin
  • SMC

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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