RNA-sequencing reveals altered skeletal muscle contraction, E3 ligases, autophagy, apoptosis, and chaperone expression in patients with critical illness myopathy
RNA-sequencing reveals altered skeletal muscle contraction, E3 ligases, autophagy, apoptosis, and chaperone expression in patients with critical illness myopathy
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DOI：
10.1186/s13395-019-0194-1
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发表时间：
2019-04-16
期刊：
影响因子：
4.9
通讯作者：
Larsson, Lars
中科院分区：
文献类型：
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作者：
Llano-Diez, Monica;Fury, Wen;Larsson, Lars
重症监护病房（ICU）患者重症肌病（CIM）与严重的骨骼肌萎缩和功能受损有关。CIM的基本机制仍然不完全清楚。为了阐明ICU CIM患者骨骼肌中转录水平上发生的生物学活性，使用RNA测序（RNA-seq）表征了基因表达谱、潜在的上游调控因子和富集途径。我们还比较了骨骼肌的基因签名在ICU患者与CIM和基因干扰的机械负荷在ICU患者的一条腿，目的是减少肌肉functions.MethodsRNA-seq的损失被用来评估胫骨前骨骼肌样本的基因表达变化7危重，固定，机械通气ICU患者与CIM和匹配的对照组。我们还检测了6名ICU CIM患者的双腿骨骼肌基因表达，其中一条腿每天机械负荷10小时，平均9天。结果在17,221个检测到的基因中，共有6257个差异表达（84%上调; P < 0.05）。
BackgroundCritical illness myopathy (CIM) is associated with severe skeletal muscle wasting and impaired function in intensive care unit (ICU) patients. The mechanisms underlying CIM remain incompletely understood. To elucidate the biological activities occurring at the transcriptional level in the skeletal muscle of ICU patients with CIM, the gene expression profiles, potential upstream regulators, and enrichment pathways were characterized using RNA sequencing(RNA-seq). We also compared the skeletal muscle gene signatures in ICU patients with CIM and genes perturbed by mechanical loading in one leg of the ICU patients, with an aim of reducing the loss of muscle function.MethodsRNA-seq was used to assess gene expression changes in tibialis anterior skeletal muscle samples from seven critically ill, immobilized, and mechanically ventilated ICU patients with CIM and matched control subjects. We also examined skeletal muscle gene expression for both legs of six ICU patients with CIM, where one leg was mechanically loaded for 10h/day for an average of 9days.ResultsIn total, 6257 of 17,221 detected genes were differentially expressed (84% upregulated; p