Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation.

Abstract

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate. However, it is unclear what factors play a role in this process. In this study, we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury. Platelet factor is an important molecule in cell apoptosis, differentiation, survival, and proliferation. Further, polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury. Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells. We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells, while exogenously applied platelet factor 4 stimulated Schwann cell proliferation and migration and neuronal axon growth. Furthermore, knocking out platelet factor 4 inhibited the proliferation of Schwann cells in injured rat sciatic nerve. These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth. Thus, platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.