Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8
Abstract After a peripheral nerve injury, Schwann cells (SCs), the myelinating glia of the peripheral nervous system, convert into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism d...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55835-9 |
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| author | Nadège Hertzog Mert Duman Maëlle Bochud Valérie Brügger-Verdon Maren Gerhards Felicia Schön Franka Dorndecker Dies Meijer Robert Fledrich Ruth Stassart Devanarayanan Siva Sankar Jörn Dengjel Sofía Raigón López Claire Jacob |
| author_facet | Nadège Hertzog Mert Duman Maëlle Bochud Valérie Brügger-Verdon Maren Gerhards Felicia Schön Franka Dorndecker Dies Meijer Robert Fledrich Ruth Stassart Devanarayanan Siva Sankar Jörn Dengjel Sofía Raigón López Claire Jacob |
| author_sort | Nadège Hertzog |
| collection | DOAJ |
| description | Abstract After a peripheral nerve injury, Schwann cells (SCs), the myelinating glia of the peripheral nervous system, convert into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism depends however on the time needed for axons to regrow. Here, we show that ablation of histone deacetylase 8 (HDAC8) in SCs accelerates the regrowth of sensory axons and sensory function recovery. We found that HDAC8 is specifically expressed in sensory SCs and regulates the E3 ubiquitin ligase TRAF7, which destabilizes hypoxia-inducible factor 1-alpha (HIF1α) and counteracts the phosphorylation and upregulation of c-Jun, a major inducer of the repair SC phenotype. Our study indicates that this phenotype switch is regulated by different mechanisms in sensory and motor SCs and is accelerated by HDAC8 downregulation, which promotes sensory axon regeneration and sensory function recovery. |
| format | Article |
| id | doaj-art-5307dc82057e466eaf827607ce7bf794 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-5307dc82057e466eaf827607ce7bf7942025-01-12T12:31:15ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-55835-9Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8Nadège Hertzog0Mert Duman1Maëlle Bochud2Valérie Brügger-Verdon3Maren Gerhards4Felicia Schön5Franka Dorndecker6Dies Meijer7Robert Fledrich8Ruth Stassart9Devanarayanan Siva Sankar10Jörn Dengjel11Sofía Raigón López12Claire Jacob13Institute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University MainzInstitute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University MainzDepartment of Biology, University of FribourgDepartment of Biology, University of FribourgInstitute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University MainzInstitute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University MainzInstitute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University MainzCenter for Discovery Brain Sciences, University of EdinburghPaul Flechsig Institute, Center of Neuropathology and Brain Sciences, University of LeipzigPaul Flechsig Institute, Center of Neuropathology and Brain Sciences, University of LeipzigDepartment of Biology, University of FribourgDepartment of Biology, University of FribourgInstitute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University MainzInstitute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University MainzAbstract After a peripheral nerve injury, Schwann cells (SCs), the myelinating glia of the peripheral nervous system, convert into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism depends however on the time needed for axons to regrow. Here, we show that ablation of histone deacetylase 8 (HDAC8) in SCs accelerates the regrowth of sensory axons and sensory function recovery. We found that HDAC8 is specifically expressed in sensory SCs and regulates the E3 ubiquitin ligase TRAF7, which destabilizes hypoxia-inducible factor 1-alpha (HIF1α) and counteracts the phosphorylation and upregulation of c-Jun, a major inducer of the repair SC phenotype. Our study indicates that this phenotype switch is regulated by different mechanisms in sensory and motor SCs and is accelerated by HDAC8 downregulation, which promotes sensory axon regeneration and sensory function recovery.https://doi.org/10.1038/s41467-025-55835-9 |
| spellingShingle | Nadège Hertzog Mert Duman Maëlle Bochud Valérie Brügger-Verdon Maren Gerhards Felicia Schön Franka Dorndecker Dies Meijer Robert Fledrich Ruth Stassart Devanarayanan Siva Sankar Jörn Dengjel Sofía Raigón López Claire Jacob Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8 Nature Communications |
| title | Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8 |
| title_full | Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8 |
| title_fullStr | Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8 |
| title_full_unstemmed | Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8 |
| title_short | Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8 |
| title_sort | hypoxia induced conversion of sensory schwann cells into repair cells is regulated by hdac8 |
| url | https://doi.org/10.1038/s41467-025-55835-9 |
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