Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.

Following peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype, a process dependent upon c-Jun transcription factor activation. Unfortunately, axonal regeneration is greatly impaired in aged organisms and follow...

ver descrição completa

Detalhes bibliográficos
Autores: Fuentes-Flores A, Geronimo-Olvera C, Girardi K, Necuñir-Ibarra D, Patel SK, Bons J, Wright MC, Geschwind D, Hoke A, Gomez-Sanchez JA, Schilling B, Rebolledo DL, Campisi J, Court FA
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositório:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p9958
Acesso em linha:https://isabial.portalinvestigacion.com/publicaciones9958
https://www.embopress.org/doi/full/10.15252/emmm.202317907
Access Level:Acceso aberto
Palavra-chave:Schwann cell
aging
chronic denervation
nerve regeneration
senescence
id ES_c9f2db2d01b2d97b4e5ddca965b2c490
oai_identifier_str oai:isabial.fundanetsuite.com:p9958
network_acronym_str ES
network_name_str España
repository_id_str
spelling Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.Fuentes-Flores AGeronimo-Olvera CGirardi KNecuñir-Ibarra DPatel SKBons JWright MCGeschwind DHoke AGomez-Sanchez JASchilling BRebolledo DLCampisi JCourt FASchwann cellagingchronic denervationnerve regenerationsenescenceFollowing peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype, a process dependent upon c-Jun transcription factor activation. Unfortunately, axonal regeneration is greatly impaired in aged organisms and following chronic denervation, which can lead to poor clinical outcomes. While diminished c-Jun expression in SCs has been associated with regenerative failure, it is unclear whether the inability to maintain a repair state is associated with the transition into an axonal growth inhibition phenotype. We here find that reparative SCs transition into a senescent phenotype, characterized by diminished c-Jun expression and secretion of inhibitory factors for axonal regeneration in aging and chronic denervation. In both conditions, the elimination of senescent SCs by systemic senolytic drug treatment or genetic targeting improved nerve regeneration and functional recovery, increased c-Jun expression and decreased nerve inflammation. This work provides the first characterization of senescent SCs and their influence on axonal regeneration in aging and chronic denervation, opening new avenues for enhancing regeneration and functional recovery after peripheral nerve injuries.SPRINGERNATURE2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones9958https://www.embopress.org/doi/full/10.15252/emmm.202317907EMBO Molecular MedicineISSN: 17574676ISSNe: 17574684reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p99582026-06-12T10:20:37Z
dc.title.none.fl_str_mv Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.
title Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.
spellingShingle Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.
Fuentes-Flores A
Schwann cell
aging
chronic denervation
nerve regeneration
senescence
title_short Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.
title_full Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.
title_fullStr Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.
title_full_unstemmed Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.
title_sort Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.
dc.creator.none.fl_str_mv Fuentes-Flores A
Geronimo-Olvera C
Girardi K
Necuñir-Ibarra D
Patel SK
Bons J
Wright MC
Geschwind D
Hoke A
Gomez-Sanchez JA
Schilling B
Rebolledo DL
Campisi J
Court FA
author Fuentes-Flores A
author_facet Fuentes-Flores A
Geronimo-Olvera C
Girardi K
Necuñir-Ibarra D
Patel SK
Bons J
Wright MC
Geschwind D
Hoke A
Gomez-Sanchez JA
Schilling B
Rebolledo DL
Campisi J
Court FA
author_role author
author2 Geronimo-Olvera C
Girardi K
Necuñir-Ibarra D
Patel SK
Bons J
Wright MC
Geschwind D
Hoke A
Gomez-Sanchez JA
Schilling B
Rebolledo DL
Campisi J
Court FA
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Schwann cell
aging
chronic denervation
nerve regeneration
senescence
topic Schwann cell
aging
chronic denervation
nerve regeneration
senescence
description Following peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype, a process dependent upon c-Jun transcription factor activation. Unfortunately, axonal regeneration is greatly impaired in aged organisms and following chronic denervation, which can lead to poor clinical outcomes. While diminished c-Jun expression in SCs has been associated with regenerative failure, it is unclear whether the inability to maintain a repair state is associated with the transition into an axonal growth inhibition phenotype. We here find that reparative SCs transition into a senescent phenotype, characterized by diminished c-Jun expression and secretion of inhibitory factors for axonal regeneration in aging and chronic denervation. In both conditions, the elimination of senescent SCs by systemic senolytic drug treatment or genetic targeting improved nerve regeneration and functional recovery, increased c-Jun expression and decreased nerve inflammation. This work provides the first characterization of senescent SCs and their influence on axonal regeneration in aging and chronic denervation, opening new avenues for enhancing regeneration and functional recovery after peripheral nerve injuries.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones9958
https://www.embopress.org/doi/full/10.15252/emmm.202317907
url https://isabial.portalinvestigacion.com/publicaciones9958
https://www.embopress.org/doi/full/10.15252/emmm.202317907
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SPRINGERNATURE
publisher.none.fl_str_mv SPRINGERNATURE
dc.source.none.fl_str_mv EMBO Molecular Medicine
ISSN: 17574676
ISSNe: 17574684
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419436597837824
score 15,81155

Registros relacionados