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Connexin 50 modulates Sox2 expression in spinal-cord-derived ependymal stem/progenitor cells

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Abstract

Ion channels included in the family of Connexins (Cx) have been reported to influence the secondary expansion of traumatic spinal cord injury (SCI) and neuropathic pain following SCI. However, Cxs also contribute to spinal cord neurogenesis during the remyelinating process and functional recovery after SCI. Certain Cxs have been recently related to the control of cell proliferation and the differentiation of neuronal progenitors. Adult spinal-cord-derived ependymal stem progenitor cells (epSPC) show high expression levels of Cx50 in non-pathological conditions and lower expression when they actively proliferate after injury (epSPCi). We explore the role of Cx50 in the ependymal population in the modulation of Sox2, a crucial factor of neural progenitor self-renewal and a promising target for promoting neuronal-cell-fate induction for neuronal tissue repair. Short-interfering-RNA ablation or over-expression of Cx50 regulates the expression of Sox2 in both epSPC and epSPCi. Interestingly, Cx50 and Sox2 co-localize at the nucleus indicating a potential role for this ion channel beyond cell-to-cell communication in the spinal cord. In vivo and in vitro experiments with Clotrimazole, a specific pharmacological modulator of Cx50, show the convergent higher expression of Cx50 and Sox2 in the isolated epSPC/epSPCi and in spinal cord tissue. Therefore, the pharmacological modulation of Cx50 might constitute an interesting mechanism for Sox2 induction to modulate the endogenous regenerative potential of neuronal tissue with a potential application in regenerative therapies.

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Acknowledgments

We thank María Teresa Calvo-Fernandez, Fabrice Durupt, Francesca De Giorgio, Maravillas Mellado, Erik Lopez-Mocholi and Alicia García-Jareño for their excellent technical support.

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Authors and Affiliations

  1. Neuronal and Tissue Regeneration Laboratory, Centro de Investigación Príncipe Felipe, Valencia, E-46012, Spain

    Francisco Javier Rodriguez-Jimenez, Ana Alastrue & Victoria Moreno-Manzano

  2. Spebo Medical, Leskovac, Serbia

    Miodrag Stojkovic

  3. Human Genetics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Miodrag Stojkovic

  4. Stem cell Therapies in Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe, Valencia, E-46012, Spain

    Slaven Erceg

Authors
  1. Francisco Javier Rodriguez-Jimenez
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  2. Ana Alastrue
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  3. Miodrag Stojkovic
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  4. Slaven Erceg
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  5. Victoria Moreno-Manzano
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Correspondence to Victoria Moreno-Manzano.

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The authors declare that they have no conflicts of interest.

Ethical approval

All applicable international and/or national guidelines for the care and use of animlas were followed. All procedures performed in studies involving animlas were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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This study was funded by grants CONSOLIDER-INGENIO 2010 CSD2008-00005 from the Ministerio de Economía y Competitividad and PI10/01683 and PI13/00319 from the Instituto de Salud Carlos III.

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Rodriguez-Jimenez, F.J., Alastrue, A., Stojkovic, M. et al. Connexin 50 modulates Sox2 expression in spinal-cord-derived ependymal stem/progenitor cells. Cell Tissue Res 365, 295–307 (2016). https://doi.org/10.1007/s00441-016-2421-y

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  • DOI: https://doi.org/10.1007/s00441-016-2421-y

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