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Jun O-GlcNAcylatSchwann cell O-GlcNAcylation promotes peripheral nerve remyelination via attenuation of the AP-1 transcription factor JUNion promotes peripheral nerve remyelination after nerve injury

ABSTRACT: Jun O-GlcNAcylatSchwann cell O-GlcNAcylation promotes peripheral nerve remyelination via attenuation of the AP-1 transcription factor JUNion promotes peripheral nerve remyelination after nerve injury

PROVIDER: PRJNA474599 | ENA |

REPOSITORIES: ENA

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Schwann cell O-GlcNAcylation promotes peripheral nerve remyelination via attenuation of the AP-1 transcription factor JUN.

Project description:Schwann cells (SCs), the glia of the peripheral nervous system, play an essential role in nerve regeneration. Upon nerve injury, SCs are reprogrammed into unique "repair SCs," and these cells remove degenerating axons/myelin debris, promote axonal regrowth, and ultimately remyelinate regenerating axons. The AP-1 transcription factor JUN is promptly induced in SCs upon nerve injury and potently mediates this injury-induced SC plasticity; however, the regulation of these JUN-dependent SC injury responses is unclear. Previously, we produced mice with a SC-specific deletion of O-GlcNAc transferase (OGT). This enzyme catalyzes O-GlcNAcylation, a posttranslational modification that is influenced by the cellular metabolic state. Mice lacking OGT in SCs develop a progressive demyelinating peripheral neuropathy. Here, we investigated the nerve repair process in OGT-SCKO mutant mice and found that the remyelination of regenerating axons is severely impaired. Gene expression profiling of OGT-SCKO SCs revealed that the JUN-dependent SC injury program was elevated in the absence of injury and failed to shut down at the appropriate time after injury. This aberrant JUN activity results in abnormalities in repair SC function and redifferentiation and prevents the timely remyelination. This aberrant nerve injury response is normalized in OGT-SCKO mice with reduced Jun gene dosage in SCs. Mechanistically, OGT O-GlcNAcylates JUN at multiple sites, which then leads to an attenuation of AP-1 transcriptional activity. Together, these results highlight the metabolic oversight of the nerve injury response via the regulation of JUN activity by O-GlcNAcylation, a pathway that could be important in the neuropathy associated with diabetes and aging.

| S-EPMC6077742 | biostudies-literature

Jun O-GlcNAcylatSchwann cell O-GlcNAcylation promotes peripheral nerve remyelination via attenuation of the AP-1 transcription factor JUNion promotes peripheral nerve remyelination after nerve injury

Project description:To uncover abnormally regulated genes in OGT-KO SCs, we performed gene expression profiling experiments using sciatic nerves from 1-month-old OGT-SCKO and wildtype mice.

2018-06-06 | GSE115333 | GEO

Muscle-resident mesenchymal progenitors sense and repair peripheral nerve injury via the GDNF-BDNF axis

Project description:Fibro-adipogenic progenitors (FAPs) are muscle-resident mesenchymal progenitors that can contribute to muscle tissue homeostasis and regeneration, as well as postnatal maturation and lifelong maintenance of the neuromuscular system. Recently, traumatic injury to the peripheral nerve was shown to activate FAPs, suggesting that FAPs can respond to nerve injury. However, questions of how FAPs can sense the anatomically distant peripheral nerve injury and whether FAPs can directly contribute to nerve regeneration remained unanswered. Here, utilizing single-cell transcriptomics and mouse models, we discovered that a subset of FAPs expressing GDNF receptors Ret and Gfra1 can respond to peripheral nerve injury by sensing GDNF secreted by Schwann cells. Upon GDNF sensing, this subset becomes activated and expresses Bdnf. FAP-specific inactivation of Bdnf (Prrx1-Cre; Bdnf-fl/fl) resulted in delayed nerve regeneration owing to defective remyelination, indicating that GDNF-sensing FAPs play an important role in the remyelination process during peripheral nerve regeneration. In aged mice, significantly reduced Bdnf expression in FAPs was observed upon nerve injury, suggesting the clinical relevance of FAP-derived BDNF in the age-related delays in nerve regeneration. Collectively, our study revealed the previously unidentified role of FAPs in peripheral nerve regeneration, and the molecular mechanism behind FAPs’ response to peripheral nerve injury.

2024-07-30 | GSE250436 | GEO

Netrin-1 engineered endothelial cell exosomes induce the formation of pre-regenerative niche to accelerate peripheral nerve repair

Project description:The formation of vascular niche is pivotal during the early stage of peripheral nerve regeneration. This antecedent angiogenesis meets the nutrient requirements for subsequent rapid axon regeneration and remyelination. Nevertheless, the mechanisms of vascular niche in the regulation of peripheral nerve remain unclear. The axon guidance molecule Netrin-1 (NTN1) is widely expressed in peripheral nerves and particularly was found up-regulated in sciatic nerve stump after peripheral nerve injury (PNI). Herein, we demonstrated that NTN1-high endothelial cells (NTN1+ECs) were the critical component of vascular niche, fostering angiogenesis, axon regeneration and repair-related phenotypes. And we also found that NTN1+ECs derived exosomes (NTN1 EC-EXO) were involved in the formation of vascular niche as a critical role. Multi-omics analysis further verified that NTN1 EC-EXO carried a low-level expression of let7a-5p and activated key pathways associated with niche formation including focal adhesion, axon guidance, PI3K-AKT signaling pathway and mTOR signaling pathway. Taken together, our findings suggested the potential construction of a pre-regenerative niche induced by NTN1 EC-EXO, thereby establishing a conductive microenvironment for nerve repair and facilitating the functional recovery after PNI in the early injury phase.

2024-05-17 | PXD051130 | Pride

Vagus Nerve Stimulation enhances remyelination and decreases innate neuroinflammation in a Multiple Sclerosis rodent model.

Project description:This study investigated the effect of Vagus Nerve Stimulation (VNS) on innate neuroinflammation and remyelination in lysolecithin (LPC) induced demyelination, a preclinical model for Multiple Sclerosis (MS). In a first experiment (demyelination experiment), LPC was injected in the corpus callosum of 33 Lewis rats, inducing a demyelinated lesion, and rats were treated with either continuously-cycled VNS (cVNS) or one-minute per day VNS (1minVNS) or sham VNS, from two days before the injection until three days post-injection (dpi), when they were killed for immunohistochemistry and proteomics analysis. This timepoint corresponded with a demyelinated lesion and peak inflammation. In a second experiment (remyelination experiment), 13 rats were analogously treated with either cVNS or sham from two days before LPC injection until 11 dpi, when they were killed for tissue prelevation for immunohistochemistry and proteomics. This timepoints corresponded with partial remyelination of the lesion. For proteomics analysis, 20 rats were randomly selected, namely five cVNS and five sham rats of the demyelination experiment, and five cVNS and five sham rats of the remyelination experiment.

2024-05-10 | PXD050858 | Pride

Malignant peripheral nerve sheath tumor (MPNST) tumor samples

Project description:Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma. Comprehensive proteomic profiles of 23 MPNST tumor specimens were obtained using LC-MS/MS. Among 23 tumor specimens, 13 patients showed favorable prognosis and 10 did local recurrence/distant metastasis.

2022-12-22 | PXD030585 | JPOST Repository

RNA-seq of mouse sciatic peripheral nerve of uninjured mouse against implantation of a silicon device or peripheral nerve injury.

Project description:Foreign body reaction is one of the most important limiting factors to the clinical translation of implantable bioelectronics. The experiment compares the process of foreign body reaction, following the implantation of a silicon device in a mouse peripheral nerve, to that of peripheral nerve injury, following nerve crushing. Both processes are also compared to a naïve peripheral nerve from an uninjured mouse. The endpoints are day 1, 4, 7, 14 and 28 days.

2022-04-30 | E-MTAB-10294 | biostudies-arrayexpress

Histone methylation in rat peripheral nerve

Project description:Histone methylation in rat peripheral nerve

| PRJNA418737 | ENA

Netrin-1 engineered endothelial cell exosomes induce the formation of pre-regenerative niche to accelerate peripheral nerve repair

2024-05-16 | GSE263388 | GEO

H3K27me3 ChIP-seq in rat peripheral nerve

Project description:ChIP-seq of H3K27me3 in rat peripheral nerve was used to identify sites of polycomb repression associated with genes in Schwann cells, which constitute the majority of cells in peripheral nerve. H3K27me3 ChIP samples were prepared from rat sciatic nerve and then sequenced. Inputs for these ChIP samples have previously been submitted as samples GSM1541282 and GSM1541283 in Series GSE63103

2016-08-01 | E-GEOD-84265 | biostudies-arrayexpress

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