Hepatocyte Growth Factor (HGF) Promotes Peripheral Nerve Regeneration by Activating Repair Schwann Cells

Scientific Reports
Kyeong Ryang KoSunyoung Kim

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

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Citations

Apr 6, 2019·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Barbara Hausott, Lars Klimaschewski
Jul 14, 2020·Journal of Cellular Physiology·Yunzhong ZhangXin Tang
Apr 27, 2019·Frontiers in Cellular Neuroscience·Arul DuraikannuDouglas W Zochodne
Dec 12, 2019·Frontiers in Bioengineering and Biotechnology·Cristiana R CarvalhoRui L Reis
Feb 12, 2021·Frontiers in Molecular Neuroscience·Anjali BalakrishnanCarol Schuurmans
Nov 22, 2020·International Journal of Molecular Sciences·Hitoshi TonomuraKenji Takahashi
Aug 15, 2018·Biochemical and Biophysical Research Communications·Kyeong Ryang KoSunyoung Kim
Jul 3, 2021·International Journal of Molecular Sciences·Marina StavrouKleopas A Kleopa
Jun 29, 2021·Frontiers in Cell and Developmental Biology·Claudia DesoleTiziana Crepaldi
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Jan 7, 2022·Journal of Anatomy·Samuele NegroMichela Rigoni

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Methods Mentioned

BETA
ELISA
transmission electron microscopy
ELISAs
PCR

Software Mentioned

NICEM
Image
Image J
GraphPad Prism

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