Nox1 mediates basic fibroblast growth factor-induced migration of vascular smooth muscle cells.
OBJECTIVE
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.


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.
Schröder
Katrin
K
Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany.
Helmcke
Ina
I
Palfi
Katalin
K
Krause
Karl-Heinz
KH
Busse
Rudi
R
Brandes
Ralf P
RP
D000818:Animals; D001011:Aorta / Q000166:cytology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D019255:NADPH Oxidases / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D012680:Sensitivity and Specificity; D014162:Transfection
D017382:Reactive Oxygen Species; D016222:Fibroblast Growth Factor 2; D019255:NADPH Oxidases