FAK ANTISENSE OLIGODEOXYNUCLEOTIDES INHIBIT VASCULAR SMOOTH MUSCLE CELL MIGRATION AND ADHESION MEDIATED BY FAK-ERK1/2 SIGNALING PATHWAY

AIMTo study the effects of FAK-ERK1/2 signaling pathway and FAK antisense oligodeoxynucleotides (ODNs) on vascular smooth muscle cell (SMC) migration and adhesion stimulated by fibronectin (FN). METHODSMigration and adhesion of cultured SMCs were stimulated by different concentrations of FN, FAK, ERK1/2. And their phosphorylation were detected by immunoprecipitation and Western blot. FAK antisense ODNs were transfected into SMCs by cationic lipid to investigate its modulatory effects on tyrosine phosphorylation, SMCs migration and adhesion were also measured by modifing Boyden Chamber and morphological enumeration, respectively. RESULTS FAK were expressed when SMCs adhesion and migration were successfully simulated by FN (5, 10, 20, 40, 60 μg·mL^-1), high contents of FAK and ERK1/2 phosphorylation were detected by 20 μg·mL^-1 FN or more. FAK antisense ODNs were transfected efficiently by cationic lipid. FAK and ERK1/2 phosphorylation were inhibited magnificently after FAK antisense ODNs transfection. Cell migration stimulated by FN 10, 20, 40 and 60 μg·mL^-1 were reduced by 23.26%, 21.63%, 19.31% and 17.88% respectively (P<0.05). SMCs adhesive spreading in 5～60 μg·mL^-1 FN groups were reduced by 17.89%～27.67% (P<0.05). CONCLUSIONFAK-ERK1/2 mediated signal transduction play important roles in SMCs migration and adhesion stimulated by extracellular matrix. The process can be inhibited by FAK antisense ODNs effectively.