CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation and myelination.
CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation and myelination.
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CLC-2 是少突胶质细胞前体细胞分化和髓鞘形成的正调节剂
DOI：
10.3892/mmr.2018.8439
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发表时间：
2018-03
影响因子：
3.4
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Hou X;Zhang R;Wang J;Li Y;Li F;Zhang Y;Zheng X;Shen Y;Wang Y;Zhou L
少突胶质细胞（Oligodendrocytes，OL）是存在于中枢神经系统内的髓鞘形成细胞。少突胶质前体细胞（OPC）分化为成熟OL的受损是脱髓鞘疾病的主要原因。因此，确定OPC分化的潜在分子机制对于理解髓鞘形成和脱髓鞘过程至关重要。已经认识到各种外在和内在因素参与控制OPC分化;然而，离子通道，特别是电压门控氯离子通道（CLC）在OPC分化和髓鞘形成中的功能尚未完全了解。本研究表明，CLC-2可能是OPC分化和髓鞘形成的正调节剂。Western blotting结果显示CLC-2在OPCs和OLs中均有表达。此外，在两种类型的细胞中记录CLC-2电流（ICLC-2）。CLC-2的阻断剂GaTx 2对ICLC-2的抑制作用在OPCs中高于OL，表明CLC-2可能在OL分化中起作用。Western blotting和免疫荧光染色的结果也表明，髓鞘碱性蛋白的表达水平降低后，GaTx 2处理，表明OPCs分化为OL抑制CLC-2抑制。此外，蛋白质印迹分析后，它也表明，髓鞘蛋白阴阳1，髓鞘调节因子，Smad相互作用蛋白1和性别决定区Y-box 10的蛋白质表达的调节CLC-2抑制。综上所述，本研究的结果表明，CLC-2可能是OPC分化的正调控因子，并且能够通过控制CLC-2通道的数量和开放状态来促进髓鞘相关疾病中的髓鞘形成和修复。
Oligodendrocytes (OLs) are myelin-forming cells that are present within the central nervous system. Impaired oligodendrocyte precursor cell (OPC) differentiation into mature OLs is a major cause of demyelination diseases. Therefore, identifying the underlying molecular mechanisms of OPC differentiation is crucial to understand the processes of myelination and demyelination. It has been acknowledged that various extrinsic and intrinsic factors are involved in the control of OPC differentiation; however, the function of ion channels, particularly the voltage-gated chloride channel (CLC), in OPC differentiation and myelination are not fully understood. The present study demonstrated that CLC-2 may be a positive modulator of OPC differentiation and myelination. Western blotting results revealed that CLC-2 was expressed in both OPCs and OLs. Furthermore, CLC-2 currents (ICLC-2) were recorded in both types of cells. The inhibition of ICLC-2 by GaTx2, a blocker of CLC-2, was demonstrated to be higher in OPCs compared with OLs, indicating that CLC-2 may serve a role in OL differentiation. The results of western blotting and immunofluorescence staining also demonstrated that the expression levels of myelin basic protein were reduced following GaTx2 treatment, indicating that the differentiation of OPCs into OLs was inhibited following CLC-2 inhibition. In addition, following western blot analysis, it was also demonstrated that the protein expression of the myelin proteins yin yang 1, myelin regulatory factor, Smad-interacting protein 1 and sex-determining region Y-box 10 were regulated by CLC-2 inhibition. Taken together, the results of the present study indicate that CLC-2 may be a positive regulator of OPC differentiation and able to contribute to myelin formation and repair in myelin-associated diseases by controlling the number and open state of CLC-2 channels.
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影响因子：
4
作者：
LALOR, PA;MAPP, PI;REVELL, PA
通讯作者：
REVELL, PA
影响因子：
6.4
作者：
Billiards, Saraid S.;Haynes, Robin L.;Kinney, Hannah C.
通讯作者：
Kinney, Hannah C.
影响因子：
3.5
作者：
Makara, JK;Rappert, A;Kettenmann, H
通讯作者：
Kettenmann, H
影响因子：
25
作者：
Foldy, Csaba;Lee, Sang-Hun;Morgan, Robert J.;Soltesz, Ivan
通讯作者：
Soltesz, Ivan
影响因子：
2.7
作者：
Liu, Zijing;Hu, Xuemei;Qiu, Mengsheng
通讯作者：
Qiu, Mengsheng