Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice

Aging in the peripheral nervous system (PNS) leads to its dysfunction and lowers regenerative capacity after injury. Based on the pro-regenerative effect of hepatocyte growth factor (HGF) in injured peripheral nerves, we investigated whether this growth factor is involved in the age-related degenera...

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Main Authors: Nayeon Lee, Sunyoung Kim, Junghun Lee
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844022026998
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author Nayeon Lee
Sunyoung Kim
Junghun Lee
author_facet Nayeon Lee
Sunyoung Kim
Junghun Lee
author_sort Nayeon Lee
collection DOAJ
description Aging in the peripheral nervous system (PNS) leads to its dysfunction and lowers regenerative capacity after injury. Based on the pro-regenerative effect of hepatocyte growth factor (HGF) in injured peripheral nerves, we investigated whether this growth factor is involved in the age-related degeneration of the PNS. We observed that the capacity for nerve regeneration was significantly reduced under aging conditions as indicated by the decreased level of SCG10-positive axons. Functional recovery was also impaired. We further tested whether the HGF/c-Met pathway was involved, and the activation of the c-Met receptor upon nerve injury was significantly reduced, whereas the production of HGF protein was still comparable to that in young mice. Moreover, the phosphorylation and expression of c-Jun, a key regeneration-associated gene, was also lowered in aged animals. In addition, exogenous administration of the HGF expressing plasmid DNA significantly ameliorated the pain-like behavior in young animals, however, such analgesic activity was impaired in aged mice. These data suggested that the HGF/c-Met pathway might be involved in the age-related impairment of regenerative capacity in the PNS.
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spelling doaj.art-130b65c8b1bb481185ad5be0704b727f2022-12-22T04:35:53ZengElsevierHeliyon2405-84402022-11-01811e11411Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged miceNayeon Lee0Sunyoung Kim1Junghun Lee2School of Biological Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of KoreaSchool of Biological Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of KoreaCorresponding author.; School of Biological Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of KoreaAging in the peripheral nervous system (PNS) leads to its dysfunction and lowers regenerative capacity after injury. Based on the pro-regenerative effect of hepatocyte growth factor (HGF) in injured peripheral nerves, we investigated whether this growth factor is involved in the age-related degeneration of the PNS. We observed that the capacity for nerve regeneration was significantly reduced under aging conditions as indicated by the decreased level of SCG10-positive axons. Functional recovery was also impaired. We further tested whether the HGF/c-Met pathway was involved, and the activation of the c-Met receptor upon nerve injury was significantly reduced, whereas the production of HGF protein was still comparable to that in young mice. Moreover, the phosphorylation and expression of c-Jun, a key regeneration-associated gene, was also lowered in aged animals. In addition, exogenous administration of the HGF expressing plasmid DNA significantly ameliorated the pain-like behavior in young animals, however, such analgesic activity was impaired in aged mice. These data suggested that the HGF/c-Met pathway might be involved in the age-related impairment of regenerative capacity in the PNS.http://www.sciencedirect.com/science/article/pii/S2405844022026998HGFc-Metc-JunAxon outgrowthAging
spellingShingle Nayeon Lee
Sunyoung Kim
Junghun Lee
Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice
Heliyon
HGF
c-Met
c-Jun
Axon outgrowth
Aging
title Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice
title_full Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice
title_fullStr Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice
title_full_unstemmed Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice
title_short Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice
title_sort impairment of peripheral nerve regeneration by insufficient activation of the hgf c met c jun pathway in aged mice
topic HGF
c-Met
c-Jun
Axon outgrowth
Aging
url http://www.sciencedirect.com/science/article/pii/S2405844022026998
work_keys_str_mv AT nayeonlee impairmentofperipheralnerveregenerationbyinsufficientactivationofthehgfcmetcjunpathwayinagedmice
AT sunyoungkim impairmentofperipheralnerveregenerationbyinsufficientactivationofthehgfcmetcjunpathwayinagedmice
AT junghunlee impairmentofperipheralnerveregenerationbyinsufficientactivationofthehgfcmetcjunpathwayinagedmice