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首页> 外文期刊>Cell and Tissue Research >Connexin 50 modulates Sox2 expression in spinal-cord-derived ependymal stem/progenitor cells
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Connexin 50 modulates Sox2 expression in spinal-cord-derived ependymal stem/progenitor cells

机译:连接蛋白50调节脊髓源性室管膜干/祖细胞中Sox2表达。

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摘要

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.
机译:据报道,连接蛋白家族(Cx)中包含的离子通道会影响SCI后创伤性脊髓损伤(SCI)和神经性疼痛的继发性扩张。但是,Cxs在髓鞘再生过程中也有助于脊髓神经发生,并在SCI后恢复功能。最近,某些Cx与细胞增殖的控制和神经元祖细胞的分化有关。成年脊髓源性室管膜干祖细胞(epSPC)在非病理条件下显示高水平的Cx50表达,而在损伤后主动增殖时则较低。我们探讨了Cx50在室管膜上的人口在调节Sox2,神经祖细胞自我更新的关键因素和促进神经元细胞命运诱导神经元组织修复的有希望的目标中的作用。短干扰RNA消融或Cx50的过表达调节epSPC和epSPCi中Sox2的表达。有趣的是,Cx50和Sox2共位于细胞核,表明该离子通道的潜在作用超出了脊髓中细胞与细胞之间的通讯。使用克霉唑(Cx50的一种特定药理调节剂)进行的体内和体外实验显示,在分离的epSPC / epSPCi和脊髓组织中,Cx50和Sox2的聚合表达较高。因此,Cx50的药理学调节可能构成一个有趣的机制,用于Sox2诱导以调节神经元组织的内源性再生潜力,并可能在再生疗法中应用。

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