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Blockade of integrin beta3-FAK signaling pathway activated by osteopontin inhibits neointimal formation after balloon injury.

Authors: Han, M  Wen, JK  Zheng, B  Liu, Z  Chen, Y 
Citation: Han M, etal., Cardiovasc Pathol. 2007 Sep-Oct;16(5):283-90. Epub 2007 Jun 20.
Pubmed: (View Article at PubMed) PMID:17868879
DOI: Full-text: DOI:10.1016/j.carpath.2007.04.002

BACKGROUND: Osteopontin (OPN) promotes the migration and adhesion of vascular smooth muscle cells (VSMCs) through cell surface receptor, integrin beta3. In order to elucidate the signaling pathway by which OPN is involved in neointimal formation, we focused on integrin beta3-focal adhesion kinase (FAK) upon VSMC migration. METHODS: The integrin beta3 and FAK expression in VSMC and in neointima was detected by Western blot and immunohistochemistry staining. FAK phosphorylation induced by OPN was verified using a linear OPN 13 peptide containing RGD motif and anti-OPN antibody. The role of integrin beta3-FAK pathway in VSMC adhesion and migration induced with OPN was tested by the overexpression of FAK-related nonkinase and integrin beta3 cytoplasmic domain. RESULTS: The results showed that OPN increased integrin beta3 expression and induced rapid and transient FAK phosphorylation. Inhibition of the phosphorylation of FAK significantly suppressed VSMC migration induced by OPN. Similarly, blockade of the interaction of integrin beta3 with OPN inhibited VSMC adhesion induced by OPN. The experiment, in vivo, demonstrated that OPN expression level was consistent with neointimal thickening. Administration of anti-OPN antibody for blocking OPN function suppressed integrin beta3 and FAK expression induced by balloon injury, and neointimal thickening was inhibited. CONCLUSIONS: These data indicate that integrin beta3-FAK signaling modulates OPN-induced VSMC migration during neointimal formation.

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CRRD Object Information
CRRD ID: 4892652
Created: 2011-02-28
Species: All species
Last Modified: 2011-02-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.