CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation and myelination

Hou,Xiaolin; Zhang,Rui; Wang,Junyan; Li,Yunhong; Li,Fan; Zhang,Yan; Zheng,Xiaomin; Shen,Ying; Wang,Yin; Zhou,Liang

doi:10.3892/mmr.2018.8439

CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation and myelination

Authors:
- Xiaolin Hou
- Rui Zhang
- Junyan Wang
- Yunhong Li
- Fan Li
- Yan Zhang
- Xiaomin Zheng
- Ying Shen
- Yin Wang
- Liang Zhou
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Affiliations: Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Ningxia Key Laboratory of Cerebrocranial Diseases, Basic Medical School of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China
Published online on: January 17, 2018 https://doi.org/10.3892/mmr.2018.8439
Pages: 4515-4523
Copyright: © Hou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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