Published online before print May 31, 2007, doi: 10.1161/ATVBAHA.107.142117
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© 2007 American Heart Association, Inc.
Vascular Biology |
Nox1 Mediates Basic Fibroblast Growth Factor-Induced Migration of Vascular Smooth Muscle Cells
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.
Correspondence to Ralf P. Brandes, Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany. 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.
The role of reactive oxygen species (ROS) generated by NADPH oxidase for basic fibroblast growth factor (bFGF)-induced smooth muscle cell migration was studied. bFGF-induced migration was dependent on ROS generated from the NADPH oxidase Nox1 but not Nox4 via a pathway involving JNK and paxillin.
Key Words: oxidative stress • superoxide • NADPH
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