RNA interference targeting alpha8 integrin attenuates smooth muscle cell growth.
alpha8 integrin gene silencing has been shown to result in the stress fibre disassembly. Stress fibres are required for cell adhesion to promote passage through cell cycle. Thus, we hypothesized that alpha8 integrin gene silencing might affect vascular smooth muscle cell (VSMC) growth. Short interference RNA (siRNA) targeting alpha8 integrin in rat VSMCs resulted in reduced DNA synthesis. Moreover, siRNA-alpha8 integrin prevented thrombin-induced proliferation. RhoA plays a critical role in regulating VSMC growth. alpha8 integrin co-immunoprecipitated with RhoA and siRNA-alpha8 reduced membrane associated RhoA. Our data suggest that alpha8 integrin expression is critical for VSMC growth, which has potential implications in postangioplasty neointimal hyperplasia.
Zargham
Ramin
R
Institut de Recherches Cliniques de Montréal, Université de Montréal and Experimental Medicine Department, McGill University, 110 Avenue Des Pins Ouest, Montréal, Que., Canada. zarghar@ircm.qc.ca
Wamhoff
Brian R
BR
Thibault
Gaétan
G
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D039001:Integrin alpha Chains / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D013917:Thrombin / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D017931:DNA Primers; D039001:Integrin alpha Chains; C093856:integrin alpha8; D004247:DNA; D013917:Thrombin; D020742:rhoA GTP-Binding Protein