NERVE SPROUTING IN INNERVATED ADULT SKELETAL-MUSCLE INDUCED BY EXPOSURE TO ELEVATED LEVELS OF INSULIN-LIKE GROWTH-FACTORS
NERVE SPROUTING IN INNERVATED ADULT SKELETAL-MUSCLE INDUCED BY EXPOSURE TO ELEVATED LEVELS OF INSULIN-LIKE GROWTH-FACTORS
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DOI：
10.1083/jcb.110.4.1307
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发表时间：
1990-04-01
影响因子：
7.8
通讯作者：
GRANDES, P
中科院分区：
文献类型：
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作者：
CARONI, P;GRANDES, P
成人骨骼肌部分失神经或瘫痪后会出现神经发芽，这可能是由于非活动肌肉释放了可扩散的发芽诱导活性。胰岛素样生长因子(IGF1和IFG2)是肌源性发芽活性的候选因子，因为它们(A)在体外诱导周围神经元的轴突生长；(B)成年骨骼肌失神经或瘫痪后其mRNA水平增加数倍。我们试图确定在神经支配的成人骨骼肌中IGFS水平升高是否足以产生肌内神经生长。低浓度IGFS可诱导鸡胚脑运动神经元大量突起生长。半最大反应需要0.2 nM的IGF2或IGF1，或20 nM的胰岛素。在体外观察到类似的运动神经元突起的激素结合特性。体内成年大鼠或小鼠臀肌暴露于低剂量外源性IGF2或IGF1可导致肌内神经萌发。暴露于IGF的肌肉中的发芽数量是暴露于车辆或未处理的肌肉中的10倍，并且暴露于IGF的肌肉中有12.2%的终板(对照：2.7%)从它们生长而来。神经生长反应伴随着肌肉内神经特定生长相关蛋白GAP43水平的升高。暴露于IGF的肌肉的其他特性包括间质细胞适度增殖和间质J1免疫反应增强。这些结果表明，失神经或瘫痪肌肉中IGFS水平的升高可能触发了协调的再生反应，包括神经萌发和激活的间质细胞表达神经生长支持底物分子。
Partial denervation or paralysis of adult skeletal muscle is followed by nerve sprouting, probably due to release of diffusible sprout-inducing activity by inactive muscle. Insulin-like growth factors (IGF1 and IFG2) are candidates for muscle-derived sprouting activity, becasue (a) they induce neurite growth from peripheral neurons in vitro; and (b) their mRNA levels in adult skeletal muscle increase severalfold after denervation or paralysis. We sought to determine whether the presence of elevated levels of IGFs in innervated adult skeletal muscle was sufficient to produce intramuscular nerve growth. Low concentrations of IGFs induced massive neurite growth from enriched embryonic chick motoneurons in vitro. Half-maximal responses required 0.2 nM IGF2 or IGF1, or 20 nM insulin. Similar hormone binding properties of motoneuron processes in vitro were observed. Exposure of adult rat or mouse gluteus muscle in vivo to low quantities of exogenous IGF2 or IGF1 led to intramuscular nerve sprouting. Numbers of sprouts in IGF-exposed muscles were 10-fold higher than in vehicle-exposed or untreated muscles, and 12.2% of the end plates in IGF-exposed muscle (control: 2.7%) had sprouts growing from them. The nerve growth reaction was accompanied by elevated levels of intramuscular nerve-specific growth-associated protein GAP43. Additional properties of IGF-exposed muscle include modest proliferation of interstitial cells and elevated interstitial J1 immunoreactivity. These results suggest that elevated levels of IGFs in denervated or paralyzed muscle might trigger coordinate regenerative reactions, including nerve sprouting and expression of nerve growth-supporting substrate molecules by activated interstitial cells.