SPP1 promotes Schwann cell proliferation and survival through PKCα by binding with CD44 and αvβ3 after peripheral nerve injury

Background: Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. Results: SPP1 and PKC alpha were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKC alpha antagonist Go6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKC alpha, which suggested that SPP1 functioned through PKC alpha. Moreover, both CD44 and alpha v beta 3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or beta 3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and beta 3. Conclusion: These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKC alpha signaling pathway by binding with CD44 and alpha v beta 3. This study provides a potential therapeutic target for improving peripheral nerve recovery.