Differential Patterns of ERK and STAT3 Phosphorylation after Sciatic Nerve Transection in the Rat

Sheu, John Y.; Kulhanek, Doris; Eckenstein, F.

doi:10.1006/exnr.2000.7508

Cited by 162 publications

(165 citation statements)

References 40 publications

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“…Axons begin to grow into the distal endoneurial tubes 1 week after nerve injury [6,39,45] ; Schwann cell/axon contacts are re-established and remyelination occurs at about 2 weeks; and the proper target tissues are reinnervated at about 4 weeks after sciatic nerve injury. In this process, a large number of genes with marked up-or down-regulation were differentially expressed, indicating sustained regulation at consecutive time points, meaning regeneration/repair by means of a continuously progressive program [4,10,35] . Nerve regeneration mainly consists of nerve repair and tissue re-innervation after injury [45,46] .…”

Section: Discussionmentioning

confidence: 99%

“…The molecules that were significantly up-or down-regulated after such injury are known to modulate the signal pathways in key networks [15,[29][30][31][32] . It is supposed that the key networks play roles in Schwann cell activation and proliferation as well as WD and subsequent regeneration [33][34][35] . The data also suggested that the functional group of transcriptional regulators indicated in the changes of expression of these genes may be an essential prerequisite for peripheral nerve degeneration and/or regeneration.…”

Section: Kegg Analysis Of Genes Differentially Expressed During Wd Bamentioning

confidence: 99%

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Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

Yao

Shen

et al. 2013

Neurosci. Bull.

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Wallerian degeneration (WD) remains an important research topic. Many genes are differentially expressed during the process of WD, but the precise mechanisms responsible for these differentiations are not completely understood. In this study, we used microarrays to analyze the expression changes of the distal nerve stump at 0, 1, 4, 7, 14, 21 and 28 days after sciatic nerve injury in rats. The data revealed 6 076 differentially-expressed genes, with 23 types of expression, specifically enriched in genes associated with nerve development and axonogenesis, cytokine biosynthesis, cell differentiation, cytokine/chemokine production, neuron differentiation, cytokinesis, phosphorylation and axon regeneration. Kyoto Encyclopedia of Genes and Genomes pathway analysis gave findings related mainly to the MAPK signaling pathway, the Jak-STAT signaling pathway, the cell cycle, cytokine-cytokine receptor interaction, the p53 signaling pathway and the Wnt signaling pathway. Some key factors were NGF, MAG, CNTF, CTNNA2, p53, JAK2, PLCB1, STAT3, BDNF, PRKC, collagen II, FGF, THBS4, TNC and c-Src, which were further validated by real-time quantitative PCR, Western blot, and immunohistochemistry. Our findings contribute to a better understanding of the functional analysis of differentially-expressed genes in WD and may shed light on the molecular mechanisms of nerve degeneration and regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Kegg Analysis Of Genes Differentially Expressed During Wd Bamentioning

confidence: 99%

Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

Yao

Shen

et al. 2013

Neurosci. Bull.

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“…In line with the possibility that neuregulin-1 is involved in Schwann cell dedifferentiation, there is evidence that ERK1/2 activation could play a role in demyelination (Agthong et al, 2006;Harrisingh et al, 2004;Ogata et al, 2004;Sheu et al, 2000). Phospho-ERK1/2 levels rise rapidly in the distal stump after transection and remain high until at least 16 days later, and activation is delayed at sites distal to the transection site compared with segments adjacent to the cut site itself (Harrisingh et al, 2004;Sheu et al, 2000).…”

Section: Erk1/2 and Neuregulin-1mentioning

confidence: 95%

“…Phospho-ERK1/2 levels rise rapidly in the distal stump after transection and remain high until at least 16 days later, and activation is delayed at sites distal to the transection site compared with segments adjacent to the cut site itself (Harrisingh et al, 2004;Sheu et al, 2000). In crushed nerves, ERK1/2 phosphorylation levels remain high for up to 1 month (Agthong et al, 2006).…”

Section: Erk1/2 and Neuregulin-1mentioning

confidence: 99%

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

Jessen

Mirsky

2008

Glia

453

409

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Dedifferentiation of myelinating Schwann cells is a key feature of nerve injury and demyelinating neuropathies. We review recent evidence that this dedifferentiation depends on activation of specific intracellular signaling molecules that drive the dedifferentiation program. In particular, we discuss the idea that Schwann cells contain negative transcriptional regulators of myelination that functionally complement positive regulators such as Krox-20, and that myelination is therefore determined by a balance between two opposing transcriptional programs. Negative transcriptional regulators should be expressed prior to myelination, downregulated as myelination starts but reactivated as Schwann cells dedifferentiate following injury. The clearest evidence for a factor that works in this way relates to c-Jun, while other factors may include Notch, Sox-2, Pax-3, Id2, Krox-24, and Egr-3. The role of cell-cell signals such as neuregulin-1 and cytoplasmic signaling pathways such as the extracellular-related kinase (ERK)1/2 pathway in promoting dedifferentiation of myelinating cells is also discussed. We also review evidence that neurotrophin 3 (NT3), purinergic signaling, and nitric oxide synthase are involved in suppressing myelination. The realization that myelination is subject to negative as well as positive controls contributes significantly to the understanding of Schwann cell plasticity. Negative regulators are likely to have a major role during injury, because they promote the transformation of damaged nerves to an environment that fosters neuronal survival and axonal regrowth. In neuropathies, however, activation of these pathways is likely to be harmful because they may be key contributors to demyelination, a situation which would open new routes for clinical intervention. V V C 2008 Wiley-Liss, Inc.

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“…It has been shown that after damage to peripheral nerve, the injured nerve reacts with a peak of production of soluble NRG1-type I/II (Carroll et al, 1997;Ronchi et al, 2013;Stassart et al, 2013), ERK and AKT pathway activation (Harrisingh et al, 2004;Napoli et al, 2012;Sheu, Kulhanek, & Eckenstein, 2000) -that in vitro can be activated either by soluble NRG1 either by other factors -SC dedifferentiation and proliferation. Subsequently, NRG1 type I/II level decreases, ERK pathway is switched off, and SC remyelinate axons expressing transmembrane NRG1-type III.…”

Section: Discussionmentioning

confidence: 99%

Neuregulin 1 Role in Schwann Cell Regulation and Potential Applications to Promote Peripheral Nerve Regeneration

Gambarotta

Fregnan

Gnavi

et al. 2013

International Review of Neurobiology

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Neuregulin 1 (NRG1) is a multifunctional and versatile protein: its numerous isoforms can signal in a paracrine, autocrine or juxtacrine manner, playing a fundamental role during the development of the peripheral nervous system and during the process of nerve repair, suggesting that the treatment with NRG1 could improve functional outcome following injury. Accordingly, the use of NRG1 in vivo has already yielded encouraging results.The aim of this review is to focus on the role played by the different NRG1 isoforms during peripheral nerve regeneration and remyelination and to identify good candidates to be used for the development of tissue engineered medical devices delivering NRG1, with the final goal to promote better nerve repair.

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Differential Patterns of ERK and STAT3 Phosphorylation after Sciatic Nerve Transection in the Rat

Cited by 162 publications

References 40 publications

Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat

Negative regulation of myelination: Relevance for development, injury, and demyelinating disease

Neuregulin 1 Role in Schwann Cell Regulation and Potential Applications to Promote Peripheral Nerve Regeneration

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