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Deep Sequencing Reveals the Significant Involvement of cAMP-Related Signaling Pathways Following Sciatic Nerve Crush

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Abstract

Peripheral nerve injury and regeneration is a complex biological process jointly mediated by numerous factors. Cyclic adenosine monophosphate (cAMP) modifies the cellular behaviors of neurons and Schwann cells, and thus may contribute to peripheral nerve regeneration. Despite the importance of cAMP, the temporal and spatial expressions of genes involved in cAMP-related signaling pathways during peripheral nerve regeneration remain unclear. In the current study, by using rat sciatic nerve crush model, we analyzed previously obtained RNA deep sequencing data, explored the significance of cAMP-mediated signaling pathway and protein kinase A (PKA) signaling pathway after peripheral nerve injury, and examined the expression patterns of genes involved in these cAMP-related signaling pathways. Our results, from the genetic aspect, emphasized the critical involvement of cAMP-related signaling pathways, identified the dynamic changes of some key signaling cascades, and may help the discovery of potential therapeutic targets for peripheral nerve repair and regeneration.

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References

  1. Menorca RM, Fussell TS, Elfar JC (2013) Nerve physiology: mechanisms of injury and recovery. Hand Clin 29:317–330

    Article  PubMed  PubMed Central  Google Scholar 

  2. Campbell WW (2008) Evaluation and management of peripheral nerve injury. Clin Neurophysiol 119:1951–1965

    Article  PubMed  Google Scholar 

  3. Sunderland S (1951) A classification of peripheral nerve injuries producing loss of function. Brain 74:491–516

    Article  CAS  PubMed  Google Scholar 

  4. Gu X, Ding F, Yang Y, Liu J (2011) Construction of tissue engineered nerve grafts and their application in peripheral nerve regeneration. Prog Neurobiol 93:204–230

    Article  CAS  PubMed  Google Scholar 

  5. Shin JE, Cho Y (2017) Epigenetic regulation of axon regeneration after neural injury. Mol Cells 40:10–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Knott EP, Assi M, Pearse DD (2014) Cyclic AMP signaling: a molecular determinant of peripheral nerve regeneration. BioMed Res Int 2014:651625

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chen ZL, Yu WM, Strickland S (2007) Peripheral regeneration. Annu Rev Neurosci 30:209–233

    Article  PubMed  Google Scholar 

  8. Makwana M, Raivich G (2005) Molecular mechanisms in successful peripheral regeneration. FEBS J 272:2628–2638

    Article  CAS  PubMed  Google Scholar 

  9. Stewart HJ, Eccleston PA, Jessen KR, Mirsky R (1991) Interaction between cAMP elevation, identified growth factors, and serum components in regulating Schwann cell growth. J Neurosci Res 30:346–352

    Article  CAS  PubMed  Google Scholar 

  10. Jessen KR, Mirsky R, Morgan L (1991) Role of cyclic AMP and proliferation controls in Schwann cell differentiation. Ann NY Acad Sci 633:78–89

    Article  CAS  PubMed  Google Scholar 

  11. Aglah C, Gordon T, Posse de Chaves EI (2008) cAMP promotes neurite outgrowth and extension through protein kinase A but independently of Erk activation in cultured rat motoneurons. Neuropharmacology 55:8–17

    Article  CAS  PubMed  Google Scholar 

  12. Bacallao K, Monje PV (2015) Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination. PLoS ONE 10:e0116948

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yu B, Zhou S, Yi S, Gu X (2015) The regulatory roles of non-coding RNAs in nerve injury and regeneration. Prog Neurobiol 134:122–139

    Article  CAS  PubMed  Google Scholar 

  14. Yi S, Zhang H, Gong L, Wu J, Zha G, Zhou S, Gu X, Yu B (2015) Deep sequencing and bioinformatic analysis of lesioned sciatic nerves after crush injury. PLoS ONE 10:e0143491

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-SEq. Nat Methods 5:621–628

    Article  CAS  PubMed  Google Scholar 

  16. Oliveros JC (2007) VENNY. An interactive tool for comparing lists with Venn diagrams

  17. Chan KM, Gordon T, Zochodne DW, Power HA (2014) Improving peripheral nerve regeneration: from molecular mechanisms to potential therapeutic targets. Exp Neurol 261:826–835

    Article  CAS  PubMed  Google Scholar 

  18. Laurenza A, Sutkowski EM, Seamon KB (1989) Forskolin: a specific stimulator of adenylyl cyclase or a diterpene with multiple sites of action? Trends Pharmacol Sci 10:442–447

    Article  CAS  PubMed  Google Scholar 

  19. Kilmer SL, Carlsen RC (1984) Forskolin activation of adenylate cyclase in vivo stimulates nerve regeneration. Nature 307:455–457

    Article  CAS  PubMed  Google Scholar 

  20. Kilmer SL, Carlsen RC (1987) Chronic infusion of agents that increase cyclic AMP concentration enhances the regeneration of mammalian peripheral nerves in vivo. Exp Neurol 95:357–367

    Article  CAS  PubMed  Google Scholar 

  21. Klein HW, Kilmer S, Carlsen RC (1989) Enhancement of peripheral nerve regeneration by pharmacological activation of the cyclic AMP second messenger system. Microsurgery 10:122–125

    Article  CAS  PubMed  Google Scholar 

  22. Udina E, Ladak A, Furey M, Brushart T, Tyreman N, Gordon T (2010) Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration. Exp Neurol 223:143–152

    Article  CAS  PubMed  Google Scholar 

  23. Han PJ, Shukla S, Subramanian PS, Hoffman PN (2004) Cyclic AMP elevates tubulin expression without increasing intrinsic axon growth capacity. Exp Neurol 189:293–302

    Article  CAS  PubMed  Google Scholar 

  24. McQuarrie IG, Grafstein B, Gershon MD (1977) Axonal regeneration in the rat sciatic nerve: effect of a conditioning lesion and of dbcAMP. Brain Res 132:443–453

    Article  CAS  PubMed  Google Scholar 

  25. Walikonis RS, Poduslo JF (1998) Activity of cyclic AMP phosphodiesterases and adenylyl cyclase in peripheral nerve after crush and permanent transection injuries. J Biol Chem 273:9070–9077

    Article  CAS  PubMed  Google Scholar 

  26. Monje PV (2015) To myelinate or not to myelinate: fine tuning cAMP signaling in Schwann cells to balance cell proliferation and differentiation. Neural Regen Res 10:1936–1937

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bacallao K, Monje PV (2013) Opposing roles of PKA and EPAC in the cAMP-dependent regulation of Schwann cell proliferation and differentiation [corrected]. PLoS ONE 8:e82354

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are grateful to Professor Jie Liu at Nantong University for his help in the preparation of the manuscript. This work was supported by the Natural Science Foundation of Jiangsu Province, China (BK20150409); and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors

Contributions

SY conceived and designed the experiments. JY, SW, CW, and SY performed the experiments. JY and SY analyzed the data. SY Contributed reagents/materials/analysis tools. SY wrote the manuscript.

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Correspondence to Sheng Yi.

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The authors declare that they have no conflict of interest.

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11064_2017_2409_MOESM1_ESM.xlsx

Table S1. Differentially expressed genes in cAMP-mediated signaling pathway. The expression levels of genes in cAMP-mediated signaling pathway at 1, 4, 7, and 14 days after sciatic nerve crush were compared with 0 day and presented as log2Ratio (XLSX 35 KB)

11064_2017_2409_MOESM2_ESM.xlsx

Table S2. Differentially expressed genes in PKA signaling pathway. The expression levels of genes in PKA signaling pathway at 1, 4, 7, and 14 days after sciatic nerve crush were compared with 0 day and presented as log2Ratio (XLSX 48 KB)

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Yu, J., Wang, S., Wu, C. et al. Deep Sequencing Reveals the Significant Involvement of cAMP-Related Signaling Pathways Following Sciatic Nerve Crush. Neurochem Res 42, 3603–3611 (2017). https://doi.org/10.1007/s11064-017-2409-3

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  • DOI: https://doi.org/10.1007/s11064-017-2409-3

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