title: Connexin 50 modulates Sox2 expression in spinal-cord-derived ependymal stem/progenitor cells.
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.
authors.affiliation: Neuronal and Tissue Regeneration Laboratory, Centro de Investigación Príncipe Felipe, Valencia, E-46012, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Rodriguez-Jimenez
authors.affiliation: Neuronal and Tissue Regeneration Laboratory, Centro de Investigación Príncipe Felipe, Valencia, E-46012, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Alastrue
authors.affiliation: Spebo Medical, Leskovac, Serbia.|Human Genetics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Stojkovic
authors.affiliation: Stem cell Therapies in Neurodegenerative Diseases Laboratory, Centro de Investigación Príncipe Felipe, Valencia, E-46012, Spain.
authors.forename: Slaven
authors.initials: S
authors.lastname: Erceg
authors.affiliation: Neuronal and Tissue Regeneration Laboratory, Centro de Investigación Príncipe Felipe, Valencia, E-46012, Spain. vmorenom@cipf.es.
authors.forename: Victoria
authors.initials: V
authors.lastname: Moreno-Manzano
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology; D017630:Connexins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004805:Ependyma / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D000099264:Connexin 50
chemical_list: D015415:Biomarkers; D003022:Clotrimazole; D017630:Connexins; D055748:SOXB1 Transcription Factors; D000099264:Connexin 50
keywords: Connexins; Ependymal; Sox2; Spinal cord injury; Stem cells