STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: Potential role for STAT3 as a retrograde signaling transcription factor
STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: Potential role for STAT3 as a retrograde signaling transcription factor
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DOI：
10.1002/cne.20140
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发表时间：
2004-07-05
影响因子：
2.5
通讯作者：
MacLennan, AJ
中科院分区：
文献类型：
--
作者：
Lee, N;Neitzel, KL;MacLennan, AJ
STAT3是一种潜在的转录因子，可被质膜生长因子受体复合物激活。条件性基因破坏数据表明，它有助于周围神经损伤后颅运动神经元的存活。与此一致的是，在相同损伤后的再生过程中，成年颅运动神经元核内活化的STAT3（酪氨酸705磷酸化的STAT3）水平已被证明会升高。此处呈现的数据表明，坐骨神经损伤后，STAT3在坐骨运动神经元中受到类似但不完全相同的影响。此外，我们发现感觉神经元核内活化的STAT3也有类似的升高，从而支持了STAT3在这些细胞的存活和再生中的作用。最有趣的是，目前的数据表明，周围神经损伤会导致损伤部位轴突中的STAT3非常迅速地活化。这种反应在损伤后的前24小时内增强，并延伸回运动神经元和感觉神经元，使得磷酸化STAT3免疫反应性轴突首先在背根神经节和脊髓腹侧在神经元核内首次检测到活化的STAT3的相同损伤后时间间隔被检测到。综合这些数据，提出了一种可能性，即损伤部位活化的轴突STAT3作为一种逆行信号转录因子，促进感觉神经元和运动神经元的存活和再生。（C）2004威利 - 利斯公司
STAT3 is a latent transcription factor that is activated by plasma membrane growth factor receptor complexes. Conditional gene disruption data indicate that it contributes to the survival of cranial motor neurons after peripheral nerve lesion. In agreement, levels of activated STAT3 (Tyr705-phosphorylated STAT3) have been shown to increase in the nuclei of adult cranial motor neurons during their regeneration after the same injury. The data presented here demonstrate that STAT3 is similarly but not identically affected in sciatic motor neurons after sciatic nerve injury. In addition, we find that sensory neuron nuclei also display an analogous increase in activated STAT3, thereby supporting a role for STAT3 in the survival and regeneration of these cells. Most interesting, the present data indicate that peripheral nerve lesion leads to a very rapid activation of STAT3 in axons at the lesion site. This response increases during the first 24 hours after injury and extends back to the motor and sensory neurons such that phospho-STAT3-immunoreactive axons are first detected in the dorsal root ganglia and ventral spinal cord at the same postlesion time intervals at which the activated STAT3 is first detected in the neuronal nuclei. Together these data raise the possibility that axonal STAT3, activated at the injury site, acts as a retrograde signaling transcription factor, which promotes the survival and regeneration of both sensory and motor neurons. (C) 2004 Wiley-Liss, Inc.