ERK1/2 and AKT are vital factors in regulation of the migration of rat Schwann cells

Abstract

After peripheral nerve injury, Wallerian degeneration (WD) occurs in the distal nerve segment. During the process of degeneration, Schwann cells (SCs) dedifferentiate, proliferate and migrate to align in “bands of Büngner”, providing structural guidance and growth-promoting substrates to regenerating axons. The molecular signals that trigger SCs migration remain unclear. Here, we explored the molecular characteristics of the migration of cultured SCs prepared from rat sciatic nerves that had degenerated. The results revealed that elevated p-ERK1/2 was coupled with the migration of SCs, activated either by nerve degeneration or the addition of placenta growth factor. However, the inhibition of ERK1/2 activity, which activated the PI3K pathway, did not show a significant negative effect on SC migratory potential. Combined inhibition of ERK1/2 and AKT activity resulted in a significant decrease in SCs motility. These molecular characteristics suggest that both the ERK1/2 and AKT signals are involved in the migratory potential of SCs. It may be helpful to understand the process of nerve regeneration and perspective on promoting peripheral nerve regeneration.

Protective effect of docosahexaenoic acid on lipotoxicity‐mediated cell death in Schwann cells: Implication of PI3K/AKT and mTORC2 pathways

“…Several studies have suggested the importance of the PI3K/AKT pathway in normal Schwann cell function (Colognato & Tzvetanova, 2011;Maurel & Salzer, 2000). AKT is important for Schwann cell migration after peripheral nerve injury (Yu et al, 2015); an overexpression of AKT is sufficient to inactivate Bad and reduce apoptosis after serum withdrawal (Li, Tennekoon, Birnbaum, Marchionni, & Rutkowski, 2001). The present study shows that palmitic acid overload decreases cell viability and induces apoptosis in…”

Ionotropic glutamate receptors activate cell signaling in response to glutamate in Schwann cells

“…Because NMDA-Rs activated ERK1/2, Akt, and cell signaling factors that are known to function downstream of these kinases, NMDA-Rs may be clustered with other SC receptors that also regulate these 2 cell signaling factors simultaneously (3,43,(47)(48)(49). These SC receptors have been reported to regulate cell cycle progression during development, SC differentiation and myelination, SC migration, and transformations in SC phenotype that accompany the response to PNS injury.…”

“…We and others have shown that activation of cell signaling factors, including ERK1/2, Akt, and Rac1, promotes SC migration (3,31,43,44). We therefore studied the effects of glutamate on SC migration, as a representative metric for reporting the effects of activated cell signaling on SC physiology.…”

MicroRNA Mediated Regulation of Schwann Cell Migration and Proliferation in Peripheral Nerve Injury

“…After peripheral nerve injury, Schwann cell migrates toward regrowing axons by regulating extracellular matrix (ECM) and ECM substrates such as fibronectin and laminin [ 34 ]. Also, extracellular signal-related kinase (ERK) 1/2 and AKT are important players for migration of Schwann cell during nerve degeneration [ 35 ]. Chang et al demonstrated that neuregulin enhanced SC migration through erbB2/3- focal adhesion kinase (FAK) pathway following nerve injury [ 36 ].…”