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Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves
Author(s) -
Yamazaki Takashi,
Sabit Hemragul,
Oya Takeshi,
Ishii Yoko,
Hamashima Takeru,
Tokunaga Ayano,
Ishizawa Shin,
Jie Shen,
Kurashige Yoichi,
Matsushima Takako,
Furuta Isao,
Noguchi Makoto,
Sasahara Masakiyo
Publication year - 2009
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1529-8027.2009.00228.x
Subject(s) - protein kinase b , receptor tyrosine kinase , microbiology and biotechnology , platelet derived growth factor receptor , kinase , phosphorylation , mitogen activated protein kinase , mapk/erk pathway , pi3k/akt/mtor pathway , p38 mitogen activated protein kinases , peripheral nerve injury , axon , tyrosine phosphorylation , biology , signal transduction , cancer research , chemistry , regeneration (biology) , receptor , biochemistry , growth factor
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‐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.