Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves.
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.
Yamazaki
Takashi
T
Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.
Sabit
Hemragul
H
Oya
Takeshi
T
Ishii
Yoko
Y
Hamashima
Takeru
T
Tokunaga
Ayano
A
Ishizawa
Shin
S
Jie
Shen
S
Kurashige
Yoichi
Y
Matsushima
Takako
T
Furuta
Isao
I
Noguchi
Makoto
M
Sasahara
Masakiyo
M
D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D017479:Receptors, Platelet-Derived Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases