The Posterior Cricoarytenoid Muscle Is Spared from MuRF1-Mediated Muscle Atrophy in Mice with Acute Lung Injury
The Posterior Cricoarytenoid Muscle Is Spared from MuRF1-Mediated Muscle Atrophy in Mice with Acute Lung Injury
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DOI：
10.1371/journal.pone.0087587
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发表时间：
2014-01-31
期刊：
影响因子：
3.7
通讯作者：
Feng, Xin
中科院分区：
文献类型：
--
作者：
Files, D. Clark;Xiao, Kunhong;Feng, Xin
背景：急性肺损伤（ALI）患者骨骼肌萎缩增加了与这种危重疾病相关的发病率和死亡率。喉肌萎缩对这些结果的影响尚不清楚，尽管在重症监护病房（ICU）幸存者中声音障碍和误吸是常见的。我们在小鼠ALI模型中评估了喉内展肌（PCA，环杓后肌）、内收肌（CT，环甲肌）和肢体（EDL，指长伸肌）肌肉。方法：用大肠杆菌脂多糖灌胃成年雄性C57Bl6J小鼠（ALI小鼠）肺。采用SDS-PAGE和质谱分析四肢和喉内肌的纤维大小、类型、蛋白表达和MyHC （my球蛋白重链）组成。结果：CT及EDL肌明显萎缩，PCA未见明显变化。E3泛素连接酶肌肉环指-1蛋白（MuRF1）是该模型中已知的肢体肌肉萎缩的介质，在CT和EDL中上调，但在PCA中没有上调。基因抑制MuRF1可保护CT和EDL免受ali诱导的肌肉萎缩。MyHC-眼外（MyHC- eo）占总MyHC的27%，分布在72%的PCA肌纤维中。结论：ALI小鼠声带外展肌（PCA）中含有大量表达MyHC-EO的纤维，可避免肌肉萎缩。PCA中缺乏MuRF1表达提示了一种以前未被认识到的机制，即该肌肉免于萎缩。在ICU幸存者中观察到声带内收肌（CT）萎缩可能导致声音受损和误吸增加。进一步评估参与系统性耗损疾病的肌肉保留可能导致这些疾病的潜在治疗靶点。
Background: Skeletal muscle wasting in acute lung injury (ALI) patients increases the morbidity and mortality associated with this critical illness. The contribution of laryngeal muscle wasting to these outcomes is unknown, though voice impairments and aspiration are common in intensive care unit (ICU) survivors. We evaluated the intrinsic laryngeal abductor (PCA, posterior cricoarytenoid), adductor (CT, cricothyroid) and limb (EDL, extensor digitorum longus) muscles in a mouse model of ALI.Methods: Escherichia coli lipopolysaccharides were instilled into the lungs of adult male C57Bl6J mice (ALI mice). Limb and intrinsic laryngeal muscles were analyzed for fiber size, type, protein expression and myosin heavy chain (MyHC) composition by SDS-PAGE and mass spectroscopy.Results: Marked muscle atrophy occurred in the CT and EDL muscles, while the PCA was spared. The E3 ubiquitin ligase muscle ring finger-1 protein (MuRF1), a known mediator of limb muscle atrophy in this model, was upregulated in the CT and EDL, but not in the PCA. Genetic inhibition of MuRF1 protected the CT and EDL from ALI-induced muscle atrophy. MyHC-Extraocular (MyHC-EO) comprised 27% of the total MyHC in the PCA, distributed as hybrid fibers throughout 72% of PCA muscle fibers.Conclusion: The vocal cord abductor (PCA) contains a large proportion of fibers expressing MyHC-EO and is spared from muscle atrophy in ALI mice. The lack of MuRF1 expression in the PCA suggests a previously unrecognized mechanism whereby this muscle is spared from atrophy. Atrophy of the vocal cord adductor (CT) may contribute to the impaired voice and increased aspiration observed in ICU survivors. Further evaluation of the sparing of muscles involved in systemic wasting diseases may lead to potential therapeutic targets for these illnesses.