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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Elsevier
2022-11-01
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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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format | Article |
id | doaj.art-130b65c8b1bb481185ad5be0704b727f |
institution | Directory Open Access Journal |
issn | 2405-8440 |
language | English |
last_indexed | 2024-04-11T07:57:47Z |
publishDate | 2022-11-01 |
publisher | Elsevier |
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series | Heliyon |
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 |