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

被引:50
作者
Yamazaki, Takashi [1 ,2 ]
Sabit, Hemragul [1 ]
Oya, Takeshi [1 ,3 ]
Ishii, Yoko [1 ,3 ]
Hamashima, Takeru [1 ]
Tokunaga, Ayano [1 ]
Ishizawa, Shin [1 ,3 ]
Jie, Shen [1 ,3 ]
Kurashige, Yoichi [1 ,3 ]
Matsushima, Takako [1 ,3 ]
Furuta, Isao [2 ]
Noguchi, Makoto [2 ]
Sasahara, Masakiyo [1 ,3 ]
机构
[1] Toyama Univ, Dept Pathol, Grad Sch Med & Pharmaceut Sci Res, Toyama 9300194, Japan
[2] Toyama Univ, Dept Oral & Maxillofacial Surg, Grad Sch Med & Pharmaceut Sci Res, Toyama 9300194, Japan
[3] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama, Japan
基金
日本科学技术振兴机构;
关键词
axon; crush injury; growth factor; neurotrophin; regeneration; Schwann cell; sciatic nerve; SCHWANN-CELL PROLIFERATION; GROWTH-FACTOR; SCIATIC-NERVE; CYCLE PROGRESSION; EXPRESSION; RAT; DIFFERENTIATION; REGENERATION; INHIBITION; ERK;
D O I
10.1111/j.1529-8027.2009.00228.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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-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.
引用
收藏
页码:165 / 176
页数:12
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