FAK antisense oligodeoxynucleotides inhibit vascular smooth muscle cell migration and adhesion mediated by FAK-ERK1/2 signaling pathway.
- Author:
Hang YIN
1
;
Li-hui WANG
;
Yong HUO
;
Xu PENG
;
Chun-fang XIA
;
Chao-shu TANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Aorta; cytology; Cell Adhesion; drug effects; Cell Movement; drug effects; Cells, Cultured; Fibronectins; pharmacology; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Mitogen-Activated Protein Kinase 1; biosynthesis; metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; biosynthesis; metabolism; Muscle, Smooth, Vascular; cytology; Myocytes, Smooth Muscle; cytology; drug effects; Oligodeoxyribonucleotides, Antisense; pharmacology; Protein-Tyrosine Kinases; antagonists & inhibitors; genetics; Rats; Rats, Sprague-Dawley; Signal Transduction; Transfection
- From: Acta Pharmaceutica Sinica 2002;37(5):334-338
- CountryChina
- Language:Chinese
-
Abstract:
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.
RESULTSFAK were expressed when SMCs adhesion and migration were successfully simulated by FN (5, 10, 20, 40, 60 micrograms.mL-1), high contents of FAK and ERK1/2 phosphorylation were detected by 20 micrograms.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 micrograms.mL-1 were reduced by 23.26%, 21.63%, 19.31% and 17.88% respectively (P < 0.05). SMCs adhesive spreading in 5-60 micrograms.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.
