RT Journal Article
SR Electronic
T1 Hepatocyte growth factor is a mitogen for Schwann cells and is present in neurofibromas
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7284
OP 7290
DO 10.1523/JNEUROSCI.14-12-07284.1994
VO 14
IS 12
A1 A Krasnoselsky
A1 MJ Massay
A1 MC DeFrances
A1 G Michalopoulos
A1 R Zarnegar
A1 N Ratner
YR 1994
UL http://www.jneurosci.org/content/14/12/7284.abstract
AB To characterize mitogens that might contribute to Schwann cell proliferation during development or in tumors, we tested the ability of hepatocyte growth factor (HGF) to stimulate Schwann cell division in vitro. HGF is a potent mitogen for purified rat Schwann cells; DNA synthesis in rat Schwann cells was stimulated 20–40-fold by 3–10 ng/ml HGF. Rat Schwann cells express c-met mRNA, encoding the HGF receptor, but not HGF mRNA, implying that HGF might act as a paracrine Schwann cell growth factor. HGF-stimulated Schwann cell proliferation differs from that of previously described Schwann cell mitogens in that its activity is abolished by forskolin and is not inhibited or potentiated by addition of transforming growth factor beta (TGF beta) or fibroblast growth factor (FGF). HGF is probably not a component of the axonal signal thought to cause Schwann cell division during development, as anti-HGF neutralizing antibodies failed to block neuron-stimulated Schwann cell proliferation. In contrast, mitogenic activity present in normal human adult nerves and in neurofibromas from patients with type 1 neurofibromatosis analyzed in the absence of forskolin is largely inhibitable by anti-HGF. Thus, HGF is a novel mitogen for Schwann cells in vitro and it is present in Schwann cell tumors, suggesting a potential role for HGF after wounding of peripheral nerves or in tumor growth.