Combined Action of GDNF and HGF Up-Regulates Axonal Growth by Increasing ERK1/2 Phosphorylation

Bull Exp Biol Med. 2019 Jul;167(3):413-417. doi: 10.1007/s10517-019-04539-4. Epub 2019 Jul 26.

Abstract

A stimulating effect of a combination of hepatocyte growth factor (HGF) and glial neurotrophic factor (GDNF) on the growth of neurites in the spinal ganglion model was demonstrated. The mechanism of neurite growth in the spinal ganglion model is associated with transactivation of HGF c-met receptor in the presence of both HGF and GDNF. The combination of HGF and GDNF significantly activated mitogenic signaling cascade mediated by protein kinases ERK1/2, which can be a mechanism for increasing the number of neurites. Our findings can be used for developing effective methods for restoring impaired peripheral nerve function after traumatic and ischemic injury using a combination of GDNF and HGF.

Keywords: glial neurotrophic factor; hepatocyte growth factor; peripheral nerve injury; regeneration.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Hepatocyte Growth Factor / metabolism*
  • MAP Kinase Signaling System / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Nerve Regeneration / physiology
  • Neurites / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-met / metabolism

Substances

  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • HGF protein, mouse
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3