TRPV4 is functionally expressed in oligodendrocyte precursor cells and increases their proliferation
TRPV4 is functionally expressed in oligodendrocyte precursor cells and increases their proliferation
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DOI：
10.1007/s00424-018-2130-3
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发表时间：
2018-05-01
影响因子：
4.5
通讯作者：
Kaneko, Shuji
中科院分区：
文献类型：
--
作者：
Ohashi, Kana;Deyashiki, Ayane;Kaneko, Shuji
少突胶质细胞是由少突胶质前体细胞分化而来的，髓鞘包裹轴突，在动作电位的快速传导和代谢支持神经元中起重要作用。阐明OPCs的增殖、迁移、分化和存活的机制对于确定中枢神经系统疾病的病因是必不可少的。然而，OPCs的这些功能与其细胞内Ca 2+信号之间的关系尚未完全阐明。在这里，我们研究了瞬时受体电位香草酸4（TRPV4），一个Ca2+渗透性通道，响应低渗透压，温和的温度，机械刺激，和内源性花生四烯酸代谢产物，在OPCs的功能。Trpv4 mRNA在体内OPCs和原代培养的大鼠OPCs中均有表达。在Ca2+成像实验中，用选择性TRPV4激动剂GSK 1016790 A处理以浓度依赖性方式诱导OPCs中细胞内Ca2+浓度的持续升高，这几乎完全被与选择性TRPV4拮抗剂HC 067047共处理所抑制。通过GSK 1016790 A刺激TRPV 4增强OPC增殖，其通过与HC 067047、细胞内Ca 2+螯合剂BAPTA-AM和蛋白激酶C抑制剂双吲哚基马来酰亚胺II共处理而被消除。相比之下，GSK 1016790 A没有显著影响OPCs的迁移或分化。总之，这些结果表明TRPV4在OPC中功能性表达，并增加这些细胞的增殖，而不影响它们分化为少突胶质细胞的能力。
Oligodendrocytes, which differentiate from oligodendrocyte precursor cells (OPCs), ensheath axons with myelin, play an essential role in rapid conduction of action potentials and metabolically support neurons. Elucidation of the mechanisms underlying the proliferation, migration, differentiation, and survival of OPCs is considered indispensable for determining the causes of central nervous system diseases. However, the relationship between these functions of OPCs and their intracellular Ca2+ signaling has not been fully elucidated. Here, we investigated the function of transient receptor potential vanilloid 4 (TRPV4), a Ca2+-permeable channel that responds to hypo-osmolarity, mild temperature, mechanical stimulation, and endogenous arachidonic acid metabolites, in OPCs. Trpv4 mRNA was detected in OPCs in vivo and in primary cultured rat OPCs. In Ca2+ imaging experiments, treatment with the selective TRPV4 agonist GSK1016790A induced sustained elevation of the intracellular Ca2+ concentration in OPCs in a concentration-dependent manner, which was almost completely suppressed by co-treatment with the selective TRPV4 antagonist HC067047. Stimulation of TRPV4 by GSK1016790A augmented OPC proliferation, which was abolished by co-treatment with HC067047, the intracellular Ca2+ chelator BAPTA-AM, and the protein kinase C inhibitor bisindolylmaleimide II. By contrast, GSK1016790A did not significantly affect the migration or differentiation of OPCs. Taken together, these results suggest that TRPV4 is functionally expressed in OPCs and increases the proliferation of these cells without affecting their ability to differentiate into oligodendrocytes.