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首页> 外文期刊>American Journal of Physiology >Impact of viral-mediated IGF-I gene transfer on skeletal muscle following cast immobilization.
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Impact of viral-mediated IGF-I gene transfer on skeletal muscle following cast immobilization.

机译：石膏固定后病毒介导的IGF-I基因转移对骨骼肌的影响。

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摘要

Insulin-like growth factor I (IGF-I) is a potent myogenic factor that plays a critical role in muscle regeneration and muscle hypertrophy. The purpose of this study was to evaluate the effect of IGF-I overexpression on the recovery of muscle size and function during reloading/reambulation after a period of cast immobilization in predominantly fast twitch muscles. In addition, we investigated concomitant molecular responses in IGF-I receptor and binding proteins (BPs). Recombinant adeno-associated virus vector for IGF-I (rAAV-IGF-IA) was injected into the anterior compartment of one of the hindlimbs of young (3 wk) C57BL6 female mice. At 20 wk of age, both hindlimbs were cast immobilized in a shortened position for 2 wk to unload the tibialis anterior (TA) and extensor longus digitorum (EDL) muscles. The TA and EDL muscles were removed bilaterally after 2 wk of cast immobilization and after 1 and 3 wk of free cage reambulation. Increases in IGF-I mRNA and protein levels with IGF-I overexpression were associated with significant increases in muscle wet weight, fiber size, and tetanic force, although overexpression did not protect against cast immobilization-induced muscle atrophy. After 1 wk of reambulation, evidence of enhanced muscle regeneration was noted in IGF-I-overexpressing muscles with an increased prevalence of central nuclei, embryonic myosin, and Pax7 positive fibers. We also observed larger relative gains in muscle size (wet weight and fiber area), but not force, during the 3-wk reambulation period in hindlimb muscles overexpressing IGF-I compared with contralateral control legs. Changes in IGFBP-5 mRNA expression during cast immobilization and reambulation paralleled those of IGF-I, whereas IGFBP-3 expression changed inversely to IGFBP-5.
机译：胰岛素样生长因子I（IGF-I）是有效的成肌因子，在肌肉再生和肌肉肥大中起关键作用。这项研究的目的是评估在快速固定的抽搐肌肉中固定固定一段时间后，在重装/重新植入过程中，IGF-I过表达对肌肉大小和功能恢复的影响。此外，我们研究了IGF-I受体和结合蛋白（BPs）中伴随的分子反应。将用于IGF-1的重组腺相关病毒载体（rAAV-IGF-IA）注射到年轻（3周）C57BL6雌性小鼠的一只后肢的前部隔室中。在20周龄时，将两个后肢固定在缩短的位置进行2周龄的固定，以卸载胫骨前（TA）和指长伸肌（EDL）的肌肉。固定固定2周后以及自由笼再造1和3周后，双侧切除TA和EDL肌肉。 IGF-I mRNA和蛋白水平随IGF-I过表达的增加与肌肉湿重，纤维大小和破伤力的显着增加有关，尽管过表达并不能防止石膏固定引起的肌肉萎缩。经过1周的重新植入后，在过表达IGF-I的肌肉中发现了增强的肌肉再生的证据，中央核，胚胎肌球蛋白和Pax7阳性纤维的患病率增加。我们还观察到，与对侧对照腿相比，过表达IGF-I的后肢肌肉在3周重做期间在肌肉大小（湿重和纤维面积）上有较大的相对增加，但没有增加力量。石膏固定和再植入过程中IGFBP-5 mRNA表达的变化与IGF-1相似，而IGFBP-3表达与IGFBP-5相反。

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