on May 31, 2007
Published online before print May 31, 2007, doi: 10.1161/ATVBAHA.107.142117
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Submitted on July 7, 2006
Accepted on May 15, 2007
Nox1 Mediates Basic Fibroblast Growth Factor-Induced Migration of Vascular Smooth Muscle Cells
Katrin Schröder ;
From the Institut für Kardiovaskuläre Physiologie (K.S., I.H., K.P., R.B. R.P.B), Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany; and The Department of Pathology, Immunology and Clinical Pathology (K.-H.K.), Centre Medical Universitaire, Geneva, Switzerland.
* To whom correspondence should be addressed. E-mail: r.brandes{at}em.uni-frankfurt.de.
Objectives--Basic fibroblast growth factor (bFGF) stimulates vascular smooth muscle cell (SMC) migration. We determined whether bFGF increases SMC reactive oxygen-species (ROS) and studied the role of ROS for SMC migration.
Methods and Results--bFGF rapidly increased rat SMC ROS formation and migration through pathways sensitive to inhibition of NADPH oxidases, PI3-kinase, protein kinase C, and Rac-1. SiRNA directed against the NADPH oxidase Nox4 impaired basal but not bFGF-induced ROS formation and did not affect migration. In contrast, siRNA against Nox1 blocked the agonist-induced ROS generation as well as the bFGF-induced migration. Agonist-induced migration was also attenuated in SMC derived from Nox1 y/- mice and transduction of Nox1 restored normal migration. Likewise, SMC outgrowth in response to bFGF was attenuated in aortic segments from Nox1 y/- mice as compared with Nox1 y/+ mice. bFGF activated JNK but not Src in a Nox1-dependent manner. Consequently, phosphorylation of the adaptor protein paxillin, which is central for migration and secretion of matrix-metalloproteinases, were dependent on Nox1 as well as JNK but not Src.
Conclusions--These data demonstrate that bFGF activates the Nox1-containing NADPH oxidase and that bFGF through a pathway involving ROS and JNK stimulates SMC migration.
Key words: oxidative stress • superoxide • NADPH
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