Activation of P2X7R inhibits proliferation and promotes the migration and differentiation of Schwann cells

Abstract In the vertebrate nervous system, myelination of nerve fibers is crucial for the rapid propagation of action potentials through saltatory conduction. Schwann cells—the main glial cells and myelinating cells of the peripheral nervous system—play a vital role in the process of nerve fiber myelination. A large amount of ATP is secreted in response to injury during the repair of peripheral nerve injuries. This ATP release subsequently the dedifferentiation of the myelinating Schwann cells into repair cells, which is necessary for the regeneration of axons. Subsequently, to restore nerve function, these repair cells redifferentiate into myelinating Schwann cells. Except for P2X4R, purine receptors such as P2X7R also play a significant role in this process. In the current study, decreased expression of P2X7R was observed immediately after sciatic nerve injury, followed by a gradual increase to the normal level of P2X7R expression. In vivo experiments showed that the activation of P2X7R using an agonist injection promoted nerve regeneration, whereas the administration of P2X7R antagonists inhibited nerve regeneration. Further, in vitro experiments supported these findings and demonstrated that P2X7R activation inhibited the proliferation of Schwann cells, but it promoted the migration and differentiation of the Schwann cells. In the current study, it was proposed that the manipulation of P2X7R expression in Schwann cells after nerve injury could be effective in facilitating nerve regrowth and remyelination. This finding would provide novel ideas and strategies for treatment programs in the future aimed at promoting nerve repair and functional recovery.