Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.
J Peripher Nerv Syst. 2009 Sep;14(3):165-76. doi: 10.1111/j.1529-8027.2009.00228.x.
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-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.
许多受体酪氨酸激酶（RTKs）及其下游的磷酸肌醇-3-激酶（PI3K）/Akt 和丝裂原激活蛋白（MAP）激酶信号通路在周围神经再生中起着关键作用。在这里，我们研究了损伤后 3 至 28 天大鼠坐骨神经远段中 PI3K/Akt 和 MAP 激酶通路以及血小板衍生生长因子受体（PDGFRs）的激活情况。在 Western blot 分析中，细胞外信号调节蛋白激酶（ERK）和 c-Jun NH2-末端激酶（JNKs）的磷酸化形式在损伤后第 3 天和第 7 天以及第 7 天和第 14 天分别显著增加。磷酸化 Akt 和 p38 从损伤后第 3 天到第 28 天持续增加。磷酸化 PDGFR-α和 -β也从第 3 天到第 14 天增加。在免疫组织化学分析中，磷酸化的 ERK 和 PDGFR-α在损伤后第 3 天的许多活化 Schwann 细胞和再生轴突中共同定位，而 PDGFR-β定位在少数梭形细胞中。检测到的 RTK 信号的时间特征似乎对 Schwann 细胞增殖和随后的再分化调节至关重要。此外，免疫组织化学研究还表明 ERK 和 PDGFR-α在轴突再生中起作用。
