DIFFERENTIAL SPATIOTEMPORAL EXPRESSION OF THE INSULIN-LIKE GROWTH-FACTOR GENES IN REGENERATING SCIATIC-NERVE
DIFFERENTIAL SPATIOTEMPORAL EXPRESSION OF THE INSULIN-LIKE GROWTH-FACTOR GENES IN REGENERATING SCIATIC-NERVE
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DOI：
10.1016/0169-328x(95)00116-a
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发表时间：
1995-12-01
期刊：
影响因子：
--
通讯作者：
ISHII, DN
中科院分区：
文献类型：
--
作者：
PU, SF;ZHUANG, HX;ISHII, DN
以往的研究表明，哺乳动物周围神经的再生依赖于内源性胰岛素样生长因子（IGFs）。本研究应用原位杂交技术检测大鼠坐骨神经挤压伤后IGF-I和IGF-II基因的时空表达。这种表达的特征在于与雪旺细胞增殖和再生过程中返回轴突中神经丝的存在有关。结果表明，IGF-I和IGF-II mRNA在挤压部位远端的坐骨神经中均增加。然而，每个转录本有一个明显不同的时间和空间分布在再生。IGF-I基因表达在神经挤压后4天内在挤压部位强烈增加。沿着挤压部位远端的神经部分，观察到中度增加，在挤压后10天达到最大水平，此后在挤压后20天降低至基线。此外，这种增加与雪旺细胞的增殖有关，并且随着含有神经丝的轴突的再生而恢复到基线。相比之下，IGF-II基因表达在损伤部位或附近没有变化，但出乎意料的是，在更远的神经肌内区域增加。这在挤压后10天开始有一个较慢的时间过程，并在挤压后20天进一步增加。这些结果表明，IGF-I和IGF-II基因受独立的信号调控，可能在神经再生过程中发挥不同的作用。他们支持IGF-I促进神经中轴突的初始发芽和随后的伸长的假设，而IGF-II增强某些轴突再生为神经的神经肌肉分支和/或神经肌肉突触的重建。
Previous studies have demonstrated that the regeneration of mammalian peripheral nerves is dependent on endogenous insulin-like growth factors (IGFs). In the present study, in situ hybridization was used to examine the temporal and spatial expression of the IGF-I and IGF-II genes in rat sciatic nerve after crush. Such expression was characterized in relation to Schwann cell proliferation and the presence of neurofilaments in returning axons during regeneration. The results show that both IGF-I and IGF-II mRNAs were increased in the sciatic nerve distal to the crush site. However, each transcript had a distinctly different temporal and spatial distribution during regeneration. IGF-I gene expression was intensely increased at the crush site within 4 days after nerve crush. Along the portion of the nerve distal to the crush site, a moderate increase was observed to reach maximal levels 10 days postcrush, and was decreased thereafter back towards baseline at 20 days postcrush. Furthermore, this increase was associated with the proliferation of Schwann cells, and the return toward baseline with the regeneration of axons containing neurofilaments. By contrast, IGF-II gene expression was unchanged at or near the site of injury, but unexpectedly was increased in more distal, intramuscular reaches of the nerves. This had a slower time course beginning 10 days postcrush, and was further increased at 20 days postcrush. These results show that the IGF-I and IGF-II genes are regulated by independent signals and probably play different roles during nerve regeneration. They support the hypotheses that IGF-I contributes to the initial sprouting and subsequent elongation of axons in nerves, whereas IGF-II enhances the regeneration of certain axons into neuromuscular branches of nerves, and/or the re-establishment of neuromuscular synapses.