Nerve growth factor stimulates fibronectin-induced fibroblast migration

Nerve growth factor (NGF), a polypeptide with well-known actions on neurons, is believed to play a role in the process of tissue repair. The aim of this study was to investigate the effect of NGF on human fetal lung fibroblast (HFL-1)-mediated type I collagen gel contraction and on chemotaxis of the cells with the use of the blind-well chamber technique. Neither coliagen gel contraction nor the chemotaxis of HFL-1 cells was affected by NGF (100 ng/mL) alone. However, NGF significantly increased HFL-1 chemotaxis to human fibronectin (20 mug/mL) and platelet-derived growth factor-BB (PDGF-BB, 10 ng/mL), by 41.8%+/-11.4% and 47.7%+/-6.6%, respectively. Checkerboard analysis showed stimulation of both chemotaxis and chemokinesis. NGF appeared to affect the rate of migration. After 12 hours, control cells had migrated as much as NGF-treated cells. The effect of NGF was blocked by the tyrosine kinase receptor A inhibitor K-252a, suggesting that the biological action of NGF on fibroblast chemotaxis is mediated through this tyrosine kinase receptor. Our findings suggest that by increasing the rate at which fibroblasts migrate in response to chemoattractants, NGF can modulate the speed and intensity of a repair response and may therefore represent a valid therapeutic target for a variety of diseases.