Hepatocyte growth factor stimulates the proliferation and migration of oligodendrocyte precursor cells

Abstract

Hepatocyte growth factor (HGF) was initially identified as a potent mitogen for mature hepatocytes and has since been found to affect a variety of cells. Evidence suggests that HGF may also influence the nervous system, in that HGF stimulates the proliferation of myelin-forming Schwann cells and olfactory ensheathing cells. However, it is not known whether HGF influences oligodendrocytes. To address this issue, oligodendrocyte precursors were obtained from neonatal rat cerebra and cultured. Immunostaining and Western blotting revealed expression of both HGF and the HGF receptor (c-Met) by cultured oligodendrocytes. When the ability of HGF to stimulate oligodendrocyte division and migration was examined, we observed that treatment with HGF (10–50 ng/ml) elicited twofold increases in oligodendrocyte precursor proliferation. HGF also enhanced oligodendrocyte precursor migration, with 2.5-fold increases in rates of migration seen after treatment for 8 hr. HGF also influenced inducing the oligodendrocyte cytoskeleton by altering patterns of F-actin and β-tubulin distribution and enhanced the expression of actin and β-tubulin. These observations show that a functional HGF/c-Met system is present in oligodendrocytes, which can influence the growth, development, and cytoskeletal organization of oligodendrocytes.