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

Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1736-43. doi: 10.1161/ATVBAHA.107.142117. Epub 2007 May 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology
  • Cell Movement / physiology*
  • Cells, Cultured
  • Fibroblast Growth Factor 2 / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Models, Animal
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism*
  • NADPH Oxidases / analysis
  • NADPH Oxidases / metabolism*
  • Probability
  • Random Allocation
  • Rats
  • Rats, Inbred Strains
  • Reactive Oxygen Species / metabolism
  • Sensitivity and Specificity
  • Transfection


  • Reactive Oxygen Species
  • Fibroblast Growth Factor 2
  • NADPH Oxidases