Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves
Takashi Yamazaki
Departments of Pathology
Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama
These authors contributed equally to this work.
Search for more papers by this authorHemragul Sabit
Departments of Pathology
These authors contributed equally to this work.
Search for more papers by this authorTakeshi Oya
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorYoko Ishii
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorShin Ishizawa
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorShen Jie
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorYoichi Kurashige
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorTakako Matsushima
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorIsao Furuta
Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama
Search for more papers by this authorMakoto Noguchi
Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama
Search for more papers by this authorCorresponding Author
Masakiyo Sasahara
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Masakiyo Sasahara, Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Sugitani 2630, Toyama, 930-0194 Japan. Tel: 81-76-434-7238; Fax: 81-76-434-5016. E-mail: [email protected]Search for more papers by this authorTakashi Yamazaki
Departments of Pathology
Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama
These authors contributed equally to this work.
Search for more papers by this authorHemragul Sabit
Departments of Pathology
These authors contributed equally to this work.
Search for more papers by this authorTakeshi Oya
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorYoko Ishii
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorShin Ishizawa
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorShen Jie
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorYoichi Kurashige
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorTakako Matsushima
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Search for more papers by this authorIsao Furuta
Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama
Search for more papers by this authorMakoto Noguchi
Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama
Search for more papers by this authorCorresponding Author
Masakiyo Sasahara
Departments of Pathology
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST), Kawaguchi, Japan
Masakiyo Sasahara, Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Sugitani 2630, Toyama, 930-0194 Japan. Tel: 81-76-434-7238; Fax: 81-76-434-5016. E-mail: [email protected]Search for more papers by this authorAbstract
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 NH2-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-α and -β were also increased from 3 to 14 days. In the immunohistological analyses, phosphorylated ERK and PDGFR-α were co-localized in many activated Schwann cells and regrowing axons 3 days after injury, while PDGFR-β 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-α in axon regeneration as well.
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