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Protein Kinase Cα Promotes Proliferation and Migration of Schwann Cells by Activating ERK Signaling Pathway
Ist Teil von
Neuroscience, 2020-05, Vol.433, p.94-107
Ort / Verlag
United States: Elsevier Ltd
Erscheinungsjahr
2020
Link zum Volltext
Quelle
Elsevier ScienceDirect Journals Complete
Beschreibungen/Notizen
•PKCα is upregulated in Schwann cells of distal nerve stumps as long as 28 days in rat sciatic nerve transection model.•PKCα promotes Schwann cell proliferation and migration in SCs.•PKCα promotes proliferation and migration via ERK 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 Büngner’s bands and secrete trophic factors during these processes. However, the underlying mechanisms remain poorly understood. Here, we found that protein kinase Cα (PKCα), a serine/threonine kinase, expressed in SCs was significantly up-regulated after PNI. Activating PKCα with phorbol 12-myristate 13-acetate (PMA), a phorbol ester binds and activates PKCα) promoted SCs proliferation and migration. While, silence of PKCα by siRNAs inhibited these processes. PD184352, an inhibitor of MEK1, reversed the effect induced by PMA on SCs. Mechanism studies revealed that PKCα functioned through activating the ERK signaling pathway. Furthermore, PKCα 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 PKCα in the mechanism of peripheral nerve degeneration as well as regeneration.