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HMGB1 enhances embryonic neural stem cell proliferation by activating the MAPK signaling pathway

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Abstract

Neural stem cells (NSCs) are involved in neural tube formation. As the high-mobility group box 1 (HMGB1) protein is involved in neurulation and is present at elevated levels in neural tube defects (NTDs) induced by hyperthermia, we have now investigated the effects of HMGB1 on proliferation, differentiation, and MAPK signaling pathways of NSCs in vitro. We constructed a lentivirus vector with HMGB1 siRNA and used it to infect NSCs. Down-regulation of HMGB1 expression was confirmed. Proliferation of NSCs was determined by MTS and nestin/BrdU double-labeling. Differentiation of NSCs was assessed using β-tubulinIII and GFAP. Knockdown of HMGB1 significantly suppressed NSC proliferation but hardly affected differentiation, which was regulated by decreased expression of MAPK signaling pathways. Thus, HMGB1 has beneficial effects on neurulation and may serve as a new target for the prevention of NTDs.

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References

  • Abraham AB, Bronstein R, Chen EI, Koller A, Ronfani L, Maletic-Savatic M, Tsirka SE (2013) Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells. Proteome Sci 11:18. doi:10.1186/1477-5956-11-18

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gong H, Zuliani P, Komuravelli A, Faeder JR, Clarke EM (2010) Analysis and verification of the HMGB1 signaling pathway. BMC Bioinform 11(Suppl 7):S10. doi:10.1186/1471-2105-11-S7-S10

    Article  Google Scholar 

  • Hayakawa K, Nakano T, Irie K, Higuchi S, Fujioka M, Orito K, Iwasaki K, Jin G, Lo EH, Mishima K, Fujiwara M (2010) Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice. J Cereb Blood Flow Metab 30:871–882

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ichi S, Nakazaki H, Boshnjaku V, Singh RM, Mania-Farnell B, Xi G, McLone DG, Tomita T, Mayanil CS (2012) Fetal neural tube stem cells from Pax3 mutant mice proliferate, differentiate, and form synaptic connections when stimulated with folic acid. Stem Cells Dev 21:321–330

    Article  CAS  PubMed  Google Scholar 

  • Kim SW, Lim CM, Kim JB, Shin JH, Lee S, Lee M, Lee JK (2011) Extracellular HMGB1 released by NMDA treatment confers neuronal apoptosis via RAGE-p38 MAPK/ERK signaling pathway. Neurotox Res 20:159–169

    Article  CAS  PubMed  Google Scholar 

  • Rao M (2004) Stem and precursor cells in the nervous system. J Neurotrauma 21:415–427

    Article  CAS  PubMed  Google Scholar 

  • Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

    Article  CAS  PubMed  Google Scholar 

  • Shie MY, Ding SJ (2013) Integrin binding and MAPK signal pathways in primary cell responses to surface chemistry of calcium silicate cements. Biomaterials 34:6589–6606

    Article  CAS  Google Scholar 

  • Stros M (2010) HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta 1799:101–113

    Article  CAS  PubMed  Google Scholar 

  • Sun W, Jiao Y, Cui B, Gao X, Xia Y, Zhao Y (2013) Immune complexes activate human endothelium involving the cell-signaling HMGB1–RAGE axis in the pathogenesis of lupus vasculitis. Lab Invest 93:626–638

    Article  CAS  PubMed  Google Scholar 

  • Turner CG, Klein JD, Wang J, Thakor D, Benedict D, Ahmed A, Teng YD, Fauza DO (2013) The amniotic fluid as a source of neural stem cells in the setting of experimental neural tube defects. Stem Cell Dev 22:548–553

    Article  CAS  Google Scholar 

  • Yang SH, Sharrocks AD, Whitmarsh AJ (2013) MAP kinase signalling cascades and transcriptional regulation. Gene 513:1–13

    Article  CAS  PubMed  Google Scholar 

  • Yu L, Guan YJ, Gao Y, Wang X (2009) Rpl30 and Hmgb1 are required for neurulation in golden hamster. Int J Neurosci 119:1076–1090

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao X, Kuja-Panula J, Rouhiainen A, Chen YC, Panula P, Rauvala H (2011) High mobility group box-1 (HMGB1; amphoterin) is required for zebrafish brain development. J Biol Chem 286:23200–23213

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (30900775), the Natural Science Foundation of Shandong Province, China (ZR2010CQ036), the Muscular Dystrophy Association (254530), and the Shandong Province Taishan Scholar Project.

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The authors declare no conflicts of interest.

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Correspondence to Li Yu, Yingjun Guan or Xin Wang.

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Li Yu, Yingjun Guan and Xin Wang have contributed equally to this study.

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Wang, L., Yu, L., Zhang, T. et al. HMGB1 enhances embryonic neural stem cell proliferation by activating the MAPK signaling pathway. Biotechnol Lett 36, 1631–1639 (2014). https://doi.org/10.1007/s10529-014-1525-2

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  • DOI: https://doi.org/10.1007/s10529-014-1525-2

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