Targeted expression of IGF-1 transgene to skeletal muscle accelerates muscle and motor neuron regeneration
Targeted expression of IGF-1 transgene to skeletal muscle accelerates muscle and motor neuron regeneration
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DOI：
10.1096/fj.02-0183fje
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发表时间：
2002-11-01
期刊：
影响因子：
4.8
通讯作者：
Schwartz, RJ
中科院分区：
文献类型：
--
作者：
Rabinovsky, ED;Gelir, E;Schwartz, RJ
目前，还没有已知的药物可以加速受损的神经和肌肉的修复。利用在骨骼肌中特异性表达人重组IGF-1的IGF-1转基因小鼠，我们验证了骨骼肌靶向基因表达IGF-1促进神经挤压损伤后运动神经再生的假说。IGF-1转基因影响神经损伤后肌肉修复过程的启动，表现为SCA-1阳性肌源性干细胞的激活增加。在IGF-1转基因小鼠中观察到卫星细胞的分化和增殖增加，表现为Cyclin D1、MyoD和肌肉生成素的表达增加。在野生型和IGF-1转基因小鼠中，肌肉生成素和烟碱型乙酰胆碱受体亚单位的表达最初都增加了，但在IGF-1转基因小鼠中恢复到正常水平的速度更快，这表明神经诱发的肌肉活动得到了挽救。在骨骼肌中表达IGF-1转基因可以加速跳跃性神经传导的恢复，通过神经丝表达检测到神经支配的增加，以及肌肉质量的更快恢复。这些研究表明，局部表达IGF-1可以促进受损神经和肌肉的修复。
Currently, there is no known medical treatment that hastens the repair of damaged nerve and muscle. Using IGF-1 transgenic mice that specifically express human recombinant IGF-1 in skeletal muscle, we test the hypotheses that targeted gene expression of IGF-1 in skeletal muscle enhances motor nerve regeneration after a nerve crush injury. The IGF-1 transgene affects the initiation of the muscle repair process after nerve injury as shown by increased activation of SCA-1positive myogenic stem cells. Increased satellite cell differentiation and proliferation are observed in IGF-1 transgenic mice, shown by increased expression of Cyclin D1, MyoD, and myogenin. Expression of myogenin and nicotinic acetylcholine receptor subunits, initially increased in both wild-type and IGF-1 transgenic mice, are restored to normal levels at a faster rate in IGF-1 transgenic mice, which indicates a rescue of nerve-evoked muscle activity. Expression of the IGF-1 transgene in skeletal muscle results in accelerated recovery of saltatory nerve conduction, increased innervation as detected by neurofilament expression, and faster recovery of muscle mass. These studies demonstrate that local expression of IGF-1 augments the repair of injured nerve and muscle.