Dataset Information

Investigation of the Hydrogen Sulfide Signaling Pathway in Schwann Cells during Peripheral Nerve Degeneration: Multi-Omics Approaches.

ABSTRACT: N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H₂S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an α,β-unsaturated carboxyl compound, on H₂S signaling in in vitro- and ex vivo-dedifferentiated Schwann cells using global proteomics (LC-MS) and transcriptomics (whole-genome and small RNA-sequencing (RNA-seq)) methods. The multi-omics analyses identified several genes and proteins related to oxidative stress, such as Sod1, Gnao1, Stx4, Hmox2, Srxn1, and Edn1. The responses to oxidative stress were transcriptionally regulated by several transcription factors, such as Atf3, Fos, Rela, and Smad2. In a functional enrichment analysis, cell cycle, oxidative stress, and lipid/cholesterol metabolism were enriched, implicating H₂S signaling in Schwann cell dedifferentiation, proliferation, and myelination. NEM-induced changes in the H₂S signaling pathway affect oxidative stress, lipid metabolism, and the cell cycle in Schwann cells. Therefore, regulation of the H₂S signaling pathway by NEM during PND could prevent Schwann cell demyelination, dedifferentiation, and proliferation.

SUBMITTER: Chun YL

PROVIDER: S-EPMC9405209 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Investigation of the Hydrogen Sulfide Signaling Pathway in Schwann Cells during Peripheral Nerve Degeneration: Multi-Omics Approaches.

Chun Yoo Lim YL Eom Won-Joon WJ Lee Jun Hyung JH Nguyen Thy N C TNC Park Ki-Hoon KH Chung Hyung-Joo HJ Seo Han H Huh Youngbuhm Y Kim Sang Hoon SH Yeo Seung Geun SG Park Wonseok W Bang Geul G Kim Jin Young JY Kim Min-Sik MS Jeong Na Young NY Jung Junyang J

Antioxidants (Basel, Switzerland) 20220819 8

N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H2S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an α,β-unsaturated carboxyl compound, on H2S signaling in in vitro- and ex vivo-dedifferentiated Schwann cells using global proteomics (LC-MS) and transcriptomics (whole-genome and small RNA-sequencin ...[more]

PMID: 36009325

Similar Datasets

Project description:UnlabelledThe rapid and dynamic transcriptional changes of Schwann cells in response to injury are critical to peripheral nerve repair, yet the epigenomic reprograming that leads to the induction of injury-activated genes has not been characterized. Polycomb Repressive Complex 2 (PRC2) catalyzes the trimethylation of lysine 27 of histone H3 (H3K27me3), which produces a transcriptionally repressive chromatin environment. We find that many promoters and/or gene bodies of injury-activated genes of mature rat nerves are occupied with H3K27me3. In contrast, the majority of distal enhancers that gain H3K27 acetylation after injury are not repressed by H3K27 methylation before injury, which is normally observed in developmentally poised enhancers. Injury induces demethylation of H3K27 in many genes, such as Sonic hedgehog (Shh), which is silenced throughout Schwann cell development before injury. In addition, experiments using a Schwann cell-specific mouse knock-out of the Eed subunit of PRC2 indicate that demethylation is a rate-limiting step in the activation of such genes. We also show that some transcription start sites of H3K27me3-repressed injury genes of uninjured nerves are bound with a mark of active promoters H3K4me3, for example, Shh and Gdnf, and the reduction of H3K27me3 results in increased trimethylation of H3K4. Our findings identify reversal of polycomb repression as a key step in gene activation after injury.Significance statementPeripheral nerve regeneration after injury is dependent upon implementation of a novel genetic program in Schwann cells that supports axonal survival and regeneration. Identifying means to enhance Schwann cell reprogramming after nerve injury could be used to foster effective remyelination in the treatment of demyelinating disorders and in identifying pathways involved in regenerative process of myelination. Although recent progress has identified transcriptional determinants of successful reprogramming of the Schwann cell transcriptome after nerve injury, our results have highlighted a novel epigenomic pathway in which reversal of the Polycomb pathway of repressive histone methylation is required for activation of a significant number of injury-induced genes.

Dataset Information

Investigation of the Hydrogen Sulfide Signaling Pathway in Schwann Cells during Peripheral Nerve Degeneration: Multi-Omics Approaches.

Publications

Investigation of the Hydrogen Sulfide Signaling Pathway in Schwann Cells during Peripheral Nerve Degeneration: Multi-Omics Approaches.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets