title: Hepatocyte growth factor protects retinal ganglion cells by increasing neuronal survival and axonal regeneration in vitro and in vivo.
abstract: Hepatocyte growth factor (HGF) is known to promote the survival and foster neuritic outgrowth of different subpopulations of CNS neurons during development. Together with its corresponding receptor c-mesenchymal-epithelial transition factor (Met), it is expressed in the developing and the adult murine, rat and human CNS. We have studied the role of HGF in paradigms of retinal ganglion cell (RGC) regeneration and cell death in vitro and in vivo. After application of recombinant HGF in vitro, survival of serum-deprived RGC-5 cells and of growth factor-deprived primary RGC was significantly increased. This was shown to be correlated to the phosphorylation of c-Met and subsequent activation of serine/threonine protein kinase Akt and MAPK downstream signalling pathways involved in neuronal survival. Furthermore, neurite outgrowth of primary RGC was stimulated by HGF. In vivo, c-Met expression in RGC was up-regulated after optic nerve axotomy lesion. Here, treatment with HGF significantly improved survival of axotomized RGC and enhanced axonal regeneration after optic nerve crush. Our data demonstrates that exogenously applied HGF has a neuroprotective and regeneration-promoting function for lesioned CNS neurons. We provide strong evidence that HGF may represent a trophic factor for adult CNS neurons, which may play a role as therapeutic target in the treatment of neurotraumatic and neurodegenerative CNS disorders.
authors: Department of Neurology, University Medicine Göttingen, R.-Koch-Strasse 40, Göttingen, Germany.
authors: Lars
authors: L
authors: Tönges
authors: Thomas
authors: T
authors: Ostendorf
authors: Fabienne
authors: F
authors: Lamballe
authors: Matthieu
authors: M
authors: Genestine
authors: Rosanna
authors: R
authors: Dono
authors: Jan-Christoph
authors: JC
authors: Koch
authors: Mathias
authors: M
authors: Bähr
authors: Flavio
authors: F
authors: Maina
authors: Paul
authors: P
authors: Lingor
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000187:drug effects*; D019771:Axotomy; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D017403:In Situ Hybridization; D051379:Mice; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D009900:Optic Nerve / Q000166:cytology / Q000473:pathology; D020221:Optic Nerve Injuries / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met