Hepatocyte growth factor protects retinal ganglion cells by increasing neuronal survival and axonal regeneration in vitro and in vivo |
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Authors: | Tönges Lars Ostendorf Thomas Lamballe Fabienne Genestine Matthieu Dono Rosanna Koch Jan-Christoph Bähr Mathias Maina Flavio Lingor Paul |
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Institution: | 1. Developmental Biology Institute of Marseille‐Luminy (IBDML), UMR 6216 CNRS, INSERM, Université de la Méditerrannée, Campus de Luminy‐Case, Marseille Cedex, France;2. Department of Neurology, University Medicine G?ttingen, G?ttingen, Germany;3. DFG Research Center for the Molecular Physiology of the Brain (CMPB), G?ttingen, Germany |
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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. |
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Keywords: | axotomy crush HGF optic nerve regeneration retinal ganglion cells |
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