Basic fibroblast growth factor (bFGF) induces vascular smooth muscle cells (VSMC) migration. We determined whether bFGF-induced cell migration requires the formation of reactive oxygen species (ROS) and studied the underlying mechanisms. bFGF rapidly increased smooth muscle ROS formation via a mechanism sensitive to the specific NADPH oxidase inhibitors apocynin and gp91ds-tat as well as to inhibition of PI3-kinase and Rac. Pre-treatment of SMC with the NADPH oxidase inhibitor gp91ds-tat also completely prevented the bFGF-induced activation of p38 MAP kinase and JNK. bFGF induced a marked migration of VSMC, which was blocked by PI3-kinase and Rac inhibitors. Moreover antioxidants as well as the specific inhibition of the NADPH oxidase prevented migration. In order to determine the NADPH oxidase homologues responsible for bFGF-induced migration, siRNA against Nox homologues were used. bFGF-induced migration was completely blocked by siRNA directed against Nox1 but remained unaffected by Nox4 siRNA. Also Nox1 siRNA, but not Nox4 or scr siRNA impaired bFGF induced phosphorylation of tyrosine residues and JNK .

These data demonstrate that bFGF activates the Nox1-containing NADPH oxidase via a pathway involving Rac and PI3-Kinase. Nox1-dependent ROS formation is cricital for bFGF-induced signaling leading to VSMC migration.