Hepatocyte Growth Factor (HGF) Promotes Peripheral Nerve Regeneration by Activating Repair Schwann Cells
Abstract
During the peripheral nerve regeneration process, a variety of neurotrophic factors play roles in nerve repair by acting on neuronal or non-neuronal cells. In this report, we investigated the role(s) of hepatocyte growth factor (HGF) and its receptor, c-met, in peripheral nerve regeneration. When mice were subjected to sciatic nerve injury, the HGF protein level was highly increased at the injured and distal sites. The level of both total and phosphorylated c-met was also highly upregulated, but almost exclusively in Schwann cells (SCs) distal from the injury site. When mice were treated with a c-met inhibitor, PHA-665752, myelin thickness and axon regrowth were decreased indicating that re-myelination was hindered. HGF promoted the migration and proliferation of cultured SCs, and also induced the expression of various genes such as GDNF and LIF, presumably by activating ERK pathways. Furthermore, exogenous supply of HGF around the injury site, by intramuscular injection of a plasmid DNA expressing human HGF, enhanced the myelin thickness and axon diameter in injured nerves. Taken together, our results indicate that HGF and c-met play important roles in Schwann cell-mediated nerve repair, and also that HGF gene transfer may pro...Continue Reading
References
Vascular and neuronal effects of VEGF in the nervous system: implications for neurological disorders
c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling.
VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions
Citations
Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit
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