Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves
Activation of MAP kinases, Akt and PDGF receptors in injured peripheral nerves
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DOI：
10.1111/j.1529-8027.2009.00228.x
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发表时间：
2009-09-01
影响因子：
3.8
通讯作者：
Sasahara, Masakiyo
中科院分区：
文献类型：
--
作者：
Yamazaki, Takashi;Sabit, Hemragul;Sasahara, Masakiyo
许多受体酪氨酸激酶(RTK)及其下游的磷脂酰肌醇-3-激酶(PI3K)/Akt和丝裂原活化蛋白(MAP)信号通路在周围神经再生中起着关键作用。在这里，我们检测了损伤后3-28天大鼠坐骨神经远端段PI3K/Akt和MAP激酶通路的激活，以及血小板衍生生长因子受体(PDGFRs)的表达。在Western印迹分析中，细胞外信号调节蛋白激酶(ERK)和c-jun氨基末端激酶(JNKs)的磷酸化形式分别在伤后3天和7天以及7天和14天显著增强。磷酸化Akt和p38在伤后3~28d持续升高。磷酸化的PDGFR-α和-β也从3天增加到14天。免疫组织化学分析显示，损伤后3d，磷酸化的ERK和PDGFR-α共定位于许多活化的雪旺细胞和再生轴突中，而PDGFR-β定位于少数梭形细胞。检测到的RTK信号的时间分布似乎对于调节雪旺细胞的增殖和随后的再分化至关重要。此外，免疫组织学研究表明ERK和PDGFR-α在轴突再生中也起着作用。
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.