Inhibition of EphA4 expression promotes Schwann cell migration and peripheral nerve regeneration.

Erythropoietin-producing hepatocellular carcinoma receptors (Ephs) and their ligands Ephrins can affect axon growth. To evaluate the efficacy of EphA4 knockdown on Schwann cell migration and peripheral nerve regeneration, we detected EphA4 levels in Schwann cells. To knock down the expression of EphA4 in Schwann cell, two independent small interfering RNAs (siRNAs) were designed, and Schwann cell migration was examined. Four days after surgery, sciatic nerve sections of wild-type (WT) and EphA4(-/-) rats were examined by immunofluorescence, and axonal outgrowth was analyzed. The EphA4 protein could be detected in Schwann cells from intact nerves. EphA4 mediates the inhibitory effect on Schwann cell migration, and EphA4 knock-down can strongly increase Schwann cell migration and peripheral nerve regeneration. Knocking-down the expression of EphA4 promotes peripheral axon growth in vivo. It may provide a potential strategy for the recovery of peripheral nerve injury.