earticle

영어

Background : Visfatin (also known as pre-B-cell colony-enhancing factor, PBEF), is a novel adipokine, such as leptin, resistin, VEGF, IL-6, and FGF-2 that reported to play an important role in proangiogenic adipokine and neuroprotective effect. Methodology/Principal Findings : We investigated whether visfatin gene expression is associated with differentiation of neuronal cells. RT-PCR analysis, morphological observations, and immunostaining revealed that CoCl2, a hypoxic mimetic agent, at 75 microM increased the expression of visfatin gene and induced neurite outgrowth in PC12 rat pheochromocytoma cells. In addition, the treatement of visfatin stimulated neurite outgrowth with the increase in the levels of nerve growth factor (NGF) mRNA and protein. NGF upregulation by visfatin was prevented by an inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Furthermore, visfatin-induced neurite outgrowth was also reduced by inhibition of ERK1/2 and NGF receptor TrkA pathways. Conclusions/Significance : Taken together, our results indicate that visfatin-induced neurite outgrowth is composed largely of two sequential steps: the induction of ERK1/2-dependent NGF gene expression by visfatin and the subsequent NGF-induced neuritogenesis. These data further suggest an integral role for visfatin-NGF signaling axis in modulating neurite outgrowth of neuronal cells.