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...
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2023 |
| Country: | España |
| Institution: | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| Repository: | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| OAI Identifier: | oai:isabial.fundanetsuite.com:p9958 |
| Online Access: | https://isabial.portalinvestigacion.com/publicaciones9958 https://www.embopress.org/doi/full/10.15252/emmm.202317907 |
| Access Level: | Open access |
| Keyword: | Schwann cell aging chronic denervation nerve regeneration senescence |
| _version_ | 1878739895572234240 |
|---|---|
| author | Fuentes-Flores A |
| 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 |
| author_browse | Bons J Campisi J Court FA Fuentes-Flores A Geronimo-Olvera C Geschwind D Girardi K Gomez-Sanchez JA Hoke A Necuñir-Ibarra D Patel SK Rebolledo DL Schilling B Wright MC |
| 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 |
| collection | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_c9f2db2d01b2d97b4e5ddca965b2c490 |
| institution | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| instname_str | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:isabial.fundanetsuite.com:p9958 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | SPRINGERNATURE |
| publisherStr | SPRINGERNATURE |
| reponame_str | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| spelling | Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury. 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 Schwann cell aging chronic denervation nerve regeneration senescence 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. SPRINGERNATURE https://isabial.portalinvestigacion.com/publicaciones9958 https://www.embopress.org/doi/full/10.15252/emmm.202317907 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | 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. |
| topic | Schwann cell aging chronic denervation nerve regeneration senescence |
| topic_facet | Schwann cell aging chronic denervation nerve regeneration senescence |
| url | https://isabial.portalinvestigacion.com/publicaciones9958 https://www.embopress.org/doi/full/10.15252/emmm.202317907 |