Increased TRPV4 expression in non-myelinating Schwann cells is associated with demyelination after sciatic nerve injury

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. Feng et al. report that TRPV4 plays an important role in Schwann cells (SCs) during nerve demyelination and remyelination in mice. Using sciatic nerve cut injury mouse models, they find that TRPV4 expression is remarkably increased in demyelinating SCs during sciatic nerve injury; and ablation of TRPV4 expression impairs the demyelinating process after nerve injury, resulting in their delayed remyelination and functional recovery.