Redox-dependent activation of PI3-kinase is involved in growth-factor- induced proliferation of fibroblasts

Proliferation of fibroblasts is important for wound healing and reparation. Platelet-derived growth factor (PDGF) is a key regulator of this activity in fibroblasts. Activation of the PDGF receptor is also associated with endogenous generation of hydrogen peroxide (H₂O₂). Here we studied the involvement of H₂O₂ in the proliferative response of fibroblasts. We found that PDGF increased cytoplasmic level of H₂O₂. This increase was blocked by apocynin, an inhibitor of the membrane assembly of NADPH oxidases. Apocynin significantly decreased PDGF-stimulated phosphorylation of Akt and the mitotic activity of fibroblasts. Apocynin did not affect the activaion of the Erk1/2 MAP-kinase pathway. These data testify in favor of the H₂O₂ effect specificity.