en
Scientific article
English

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

Published inArteriosclerosis, thrombosis, and vascular biology, vol. 27, no. 8, p. 1736-1743
Publication date2007
Abstract

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. 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.

Keywords
  • Animals
  • Aorta/cytology
  • Cell Movement/ physiology
  • Cells, Cultured
  • Fibroblast Growth Factor 2/ metabolism
  • Mice
  • Mice, Inbred Strains
  • Models, Animal
  • Muscle, Smooth, Vascular/ cytology/ metabolism
  • NADPH Oxidase/analysis/ metabolism
  • Probability
  • Random Allocation
  • Rats
  • Rats, Inbred Strains
  • Reactive Oxygen Species/metabolism
  • Sensitivity and Specificity
  • Transfection
Affiliation Not a UNIGE publication
Citation (ISO format)
SCHRODER, Katrin et al. Nox1 mediates basic fibroblast growth factor-induced migration of vascular smooth muscle cells. In: Arteriosclerosis, thrombosis, and vascular biology, 2007, vol. 27, n° 8, p. 1736–1743. doi: 10.1161/ATVBAHA.107.142117
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ISSN of the journal1079-5642
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