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- Title
Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves.
- Authors
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
- 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 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.
- Subjects
MITOGEN-activated protein kinases; PROTEIN-tyrosine kinases; PHOSPHOINOSITIDES; AXONS; CRUSH syndrome; GROWTH factors; NEUROTROPIN
- Publication
Journal of the Peripheral Nervous System, 2009, Vol 14, Issue 3, p165
- ISSN
1085-9489
- Publication type
Article
- DOI
10.1111/j.1529-8027.2009.00228.x