Feng Xiaona, Takayama Yasunori, Ohno Nobuhiko, Kanda Hirosato, Dai Yi, Sokabe Takaaki, Tominaga Makoto
Department of Physiological Sciences, SOKENDAI, Okazaki, Japan.
Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan.
Commun Biol. 2020 Nov 27;3(1):716. doi: 10.1038/s42003-020-01444-9.
Transient receptor potential vanilloid 4 (TRPV4) is a non-selective calcium-permeable cation channel that is widely expressed and activated in various neurons and glial cells in the nervous system. Schwann cells (SCs) are primary glia cells that wrap around axons to form the myelin sheath in the peripheral nervous system. However, whether TRPV4 is expressed and functions in SCs is unclear. Here, we demonstrate functional expression of TRPV4 in mouse SCs and investigated its physiological significance. Deletion of TRPV4 did not affect normal myelin development for SCs in sciatic nerves in mice. However, after sciatic nerve cut injury, TRPV4 expression levels were remarkably increased in SCs following nerve demyelination. Ablation of TRPV4 expression impaired the demyelinating process after nerve injury, resulting in delayed remyelination and functional recovery of sciatic nerves. These results suggest that local activation of TRPV4 could be an attractive pharmacological target for therapeutic intervention after peripheral nerve injury.
瞬时受体电位香草酸亚型4（TRPV4）是一种非选择性的钙通透性阳离子通道，在神经系统的各种神经元和神经胶质细胞中广泛表达并被激活。雪旺细胞（SCs）是外周神经系统中包裹轴突形成髓鞘的主要神经胶质细胞。然而，TRPV4是否在雪旺细胞中表达并发挥作用尚不清楚。在此，我们证明了TRPV4在小鼠雪旺细胞中的功能性表达，并研究了其生理意义。TRPV4的缺失并不影响小鼠坐骨神经中雪旺细胞的正常髓鞘发育。然而，在坐骨神经切断损伤后，神经脱髓鞘后雪旺细胞中TRPV4的表达水平显著增加。TRPV4表达的缺失损害了神经损伤后的脱髓鞘过程，导致坐骨神经的髓鞘再生延迟和功能恢复。这些结果表明，TRPV4的局部激活可能是外周神经损伤后治疗干预的一个有吸引力的药理学靶点。
