Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves

Abstract

A number of receptor tyrosine kinases (RTKs) and the downstream phosphatidylinositol-3-kinase (PI3K)/Akt and mitogen-activated protein (MAP) kinase signaling pathways have been critically involved in peripheral nerve regeneration. Here, we examined the activation of PI3K/Akt and MAP kinase pathways, and platelet-derived growth factor receptors (PDGFRs) in the distal segments of crushed rat sciatic nerve from 3 to 28 days after injury. In Western blot analyses, the phosphorylated forms of extracellular signal-regulated protein kinase (ERK) and c-Jun NH(2)-terminal kinases (JNKs) were highly augmented on days 3 and 7 and on days 7 and 14 after injury, respectively. Phosphorylated Akt and p38 consistently increased from 3 to 28 days after injury. Phosphorylated PDGFR-alpha and -beta were also increased from 3 to 14 days. In the immunohistological analyses, phosphorylated ERK and PDGFR-alpha were co-localized in many activated Schwann cells and regrowing axons 3 days after injury, while PDGFR-beta was localized in a few spindle-shaped cells. The detected temporal profile of RTK signaling appears to be crucial for the regulation of Schwann cell proliferation and following redifferentiation. Furthermore, the immunohistological studies suggested a role of ERK and PDGFR-alpha in axon regeneration as well.