title: Smooth Muscle-Alpha Actin Inhibits Vascular Smooth Muscle Cell Proliferation and Migration by Inhibiting Rac1 Activity.
abstract: Smooth muscle alpha-actin (SMA) is a marker for the contractile, non-proliferative phenotype of adult smooth muscle cells (SMCs). Upon arterial injury, expression of SMA and other structural proteins decreases and SMCs acquire a pro-migratory and proliferative phenotype. To what extent SMA regulates migration and proliferation of SMCs is unclear and putative signaling pathways involved remain to be elucidated. Here, we used lentiviral-mediated gene transfer and siRNA technology to manipulate expression of SMA in carotid mouse SMCs and studied effects of SMA. Overexpression of SMA results in decreased proliferation and migration and blunts serum-induced activation of the small GTPase Rac, but not RhoA. All inhibitory effects of SMA are rescued by expression of a constitutively active Rac1 mutant (V12rac1). Moreover, reduction of SMA expression by siRNA technology results in an increased activation of Rac. Taken together, this study identifies Rac1 as a downstream target for SMA to inhibit SMC proliferation and migration.
authors.affiliation: Department of Surgery and Center for Cardiovascular Biology, University of Washington, Seattle, WA, United States of America.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Surgery and Center for Cardiovascular Biology, University of Washington, Seattle, WA, United States of America.
authors.forename: Allison
authors.initials: A
authors.lastname: DeWispelaere
authors.affiliation: Department of Surgery and Center for Cardiovascular Biology, University of Washington, Seattle, WA, United States of America.
authors.forename: Frank
authors.initials: F
authors.lastname: Dastvan
authors.affiliation: Department of Pediatrics and Diabetes and Obesity Center of Excellence at the University of Washington, Seattle, WA, United States of America.
authors.forename: William R A
authors.initials: WR
authors.lastname: Osborne
authors.affiliation: Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Blechner
authors.affiliation: Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Windhorst
authors.affiliation: Department of Surgery and Center for Cardiovascular Biology, University of Washington, Seattle, WA, United States of America.
authors.forename: Guenter
authors.initials: G
authors.lastname: Daum
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D004789:Enzyme Activation; D022001:Focal Adhesions / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009154:Mutation / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D044967:Serum / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000199:Actins; C544013:alpha-smooth muscle actin, mouse; D020928:Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein