Dataset Information

SPP1 promotes Schwann cell proliferation and survival through PKC? by binding with CD44 and ?v?3 after peripheral nerve injury.

ABSTRACT: Background:Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. Results:SPP1 and PKC? were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKC? antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKC?, which suggested that SPP1 functioned through PKC?. Moreover, both CD44 and ?v?3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or ?3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and ?3. Conclusion:These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKC? signaling pathway by binding with CD44 and ?v?3. This study provides a potential therapeutic target for improving peripheral nerve recovery.

SUBMITTER: Wang JB

PROVIDER: S-EPMC7439540 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SPP1 promotes Schwann cell proliferation and survival through PKCα by binding with CD44 and αvβ3 after peripheral nerve injury.

Wang Jiang-Bo JB Zhang Zhan Z Li Jian-Nan JN Yang Tuo T Du Shuang S Cao Rang-Juan RJ Cui Shu-Sen SS

Cell & bioscience 20200820

<h4>Background</h4>Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear.<h4>Results</h4>SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs pr ...[more]

PMID: 32843960

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Project description:After peripheral nerve injury, intraperitoneal injection of folic acid improves axon quantity, increases axon density and improves electromyography results. However, the mechanisms for this remain unclear. This study explored whether folic acid promotes peripheral nerve injury repair by affecting Schwann cell function. Primary Schwann cells were obtained from rats by in vitro separation and culture. Cell proliferation, assayed using the Cell Counting Kit-8 assay, was higher in cells cultured for 72 hours with 100 mg/L folic acid compared with the control group. Cell proliferation was also higher in the 50, 100, 150, and 200 mg/L folic acid groups compared with the control group after culture for 96 hours. Proliferation was markedly higher in the 100 mg/L folic acid group compared with the 50 mg/L folic acid group and the 40 ng/L nerve growth factor group. In Transwell assays, the number of migrated Schwann cells dramatically increased after culture with 100 and 150 mg/L folic acid compared with the control group. In nerve growth factor enzyme-linked immunosorbent assays, treatment of Schwann cell cultures with 50, 100, and 150 mg/L folic acid increased levels of nerve growth factor in the culture medium compared with the control group at 3 days. The nerve growth factor concentration of Schwann cell cultures treated with 100 mg/L folic acid group was remarkably higher than that in the 50 and 150 mg/L folic acid groups at 3 days. Nerve growth factor concentration in the 10, 50, and 100 mg/L folic acid groups was higher than that in the control group at 7 days. The nerve growth factor concentration in the 50 mg/L folic acid group was remarkably higher than that in the 10 and 100 mg/L folic acid groups at 7 days. In vivo, 80 μg/kg folic acid was intraperitoneally administrated for 7 consecutive days after sciatic nerve injury. Immunohistochemical staining showed that the number of Schwann cells in the folic acid group was greater than that in the control group. We suggest that folic acid may play a role in improving the repair of peripheral nerve injury by promoting the proliferation and migration of Schwann cells and the secretion of nerve growth factors.

Project description:The 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.Peripheral 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

SPP1 promotes Schwann cell proliferation and survival through PKC? by binding with CD44 and ?v?3 after peripheral nerve injury.

Publications

SPP1 promotes Schwann cell proliferation and survival through PKCα by binding with CD44 and αvβ3 after peripheral nerve injury.

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