Protein Kinase Ca Promotes Proliferation and Migration of Schwann Cells by Activating ERK Signaling Pathway

Wallerian degeneration (WD) and axon regeneration generally take place following peripheral nerve injury (PNI). Schwann cells (SCs) and macrophages play major role in WD. SCs, acting as repair cells and primary signal mediators, dedifferentiate and proliferate to remove the debris, form Bungner's bands and secrete trophic factors during these processes. However, the underlying mechanisms remain poorly understood. Here, we found that protein kinase C alpha (PKC alpha), a serineithreonine kinase, expressed in SCs was significantly up-regulated after PNI. Activating PKC alpha with phorbol 12-myristate 13-acetate (PMA), a phorbol ester binds and activates PKC alpha) promoted SCs proliferation and migration. While, silence of PKC alpha by siRNAs inhibited these processes. PD184352, an inhibitor of MEK1, reversed the effect induced by PMA on SCs. Mechanism studies revealed that PKC alpha functioned through activating the ERK signaling pathway. Furthermore, PKC alpha also exhibited a neuroprotective role by upregulating the expression of neurotrophic factors in SCs. To sum up, this study offers novel insights for clarifying our understanding of the involvement of PKC alpha in the mechanism of peripheral nerve degeneration as well as regeneration. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.