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Resveratrol inhibits migration and Rac1 activation in EGF‐ but not PDGF‐activated vascular smooth muscle cells
Author(s) -
Kumerz Mario,
Heiss Elke H.,
Schachner Daniel,
Atanasov Atanas G.,
Dirsch Verena M.
Publication year - 2011
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201100309
Subject(s) - wortmannin , platelet derived growth factor receptor , microbiology and biotechnology , rac1 , vascular smooth muscle , epidermal growth factor , lamellipodium , growth factor , platelet derived growth factor , phosphatidylinositol , biology , pi3k/akt/mtor pathway , chemistry , signal transduction , cell migration , endocrinology , biochemistry , receptor , cell , smooth muscle
Scope: Migration of vascular smooth muscle cells (VSMC) reflects one of the initial steps in atherosclerosis. Resveratrol (RV) is suggested to mediate putative vasoprotective properties of red wine leading to the hypothesis that RV interferes with growth factor‐induced migration of VSMC. Methods and results: We show here that RV (50 μM) strongly reduces epidermal growth factor (EGF)‐ but not platelet‐derived growth factor (PDGF)‐induced VSMC migration using the wound‐healing technique. Accordingly, RV inhibited Rac1 activation and lamellipodia formation in response to EGF but not PDGF as shown by pull‐down assays and fluorescence microscopy after actin staining with phalloidin‐FITC, respectively. Since Src‐family kinases and the phosphatidylinositol‐3 kinase (PI3K) are reported to be crucial upstream mediators of Rac1 activation we examined the PI3K inhibitor wortmannin and the src kinase inhibitor SU6656 side‐by‐side with RV for their anti‐migratory potential. Whereas src inhibition abrogated both EGF‐ and PDGF‐triggered migration, wortmannin, like RV, was more effective in EGF‐ than PDGF‐activated cells, suggesting that PI3K inhibition, previously shown for RV in growth factor‐activated VSMC, contributes to the anti‐migratory effect of RV in EGF‐stimulated VSMC. Conclusion: This study is the first to discover an anti‐migratory potential of RV in EGF‐activated VSMC that is most likely mediated via Rac1 inhibition.