Microarray Analysis of Gene Expression Provides New Insights Into Denervation-Induced Skeletal Muscle Atrophy
Microarray Analysis of Gene Expression Provides New Insights Into Denervation-Induced Skeletal Muscle Atrophy
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基因表达的微阵列分析为去神经诱导的骨骼肌萎缩提供了新的见解
DOI：
10.3389/fphys.2019.01298
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发表时间：
2019-10-11
影响因子：
4
通讯作者：
Sun, Hualin
中科院分区：
文献类型：
--
作者：
Shen, Yuntian;Zhang, Ru;Sun, Hualin
去神经支配诱导骨骼肌萎缩，伴随着复杂的生化和生理变化，具有潜在的破坏性后果，甚至增加死亡率。然而，目前仍然缺乏有效的策略来治疗骨骼肌萎缩。因此，需要了解骨骼肌萎缩的分子机制，并制定新的治疗策略。在这项研究中，我们研究了大鼠周围神经损伤后失神经骨骼肌的转录谱。cDNA微阵列分析显示，坐骨神经切断后不同时间段，胫前肌中大量基因的表达存在差异。值得注意的是，去神经支配的24小时可能是触发TA肌萎缩的关键时间点。根据自组织映射（SOM）、Pearson相关热图、主成分分析（PCA）和层次聚类分析的数据，失神经支配TA肌基因表达谱的3个节点转换可能将神经损伤后0.25 h-28 d分为4个不同的转录时相。根据京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析，将这4个转录阶段分别命名为“氧化应激阶段”、“炎症阶段”、“萎缩阶段”和“萎缩性纤维化阶段”。更重要的是，坐骨神经切断后24 h的差异表达基因似乎主要涉及炎症，这可能是失神经诱导的肌肉萎缩的关键过程。总的来说，我们的研究将有助于了解失神经诱导的肌肉萎缩的分子方面，也可能为靶向治疗的时间窗口提供新的见解。
Denervation induces skeletal muscle atrophy, accompanied by complex biochemical and physiological changes, with potentially devastating outcomes even an increased mortality. Currently, however, there remains a paucity of effective strategies to treat skeletal muscle atrophy. Therefore, it is required to understand the molecular mechanisms of skeletal muscle atrophy and formulate new treatment strategies. In this study, we investigated the transcriptional profile of denervated skeletal muscle after peripheral nerve injury in rats. The cDNA microarray analysis showed that a huge number of genes in tibialis anterior (TA) muscles were differentially expressed at different times after sciatic nerve transection. Notably, the 24 h of denervation might be a critical time point for triggering TA muscle atrophy. According to the data from self-organizing map (SOM), Pearson correlation heatmap, principal component analysis (PCA), and hierarchical clustering analysis, three nodal transitions in gene expression profile of the denervated TA muscle might partition the period of 0.25 h–28 days post nerve injury into four distinct transcriptional phases. Moreover, the four transcriptional phases were designated as “oxidative stress stage”, “inflammation stage”, “atrophy stage” and “atrophic fibrosis stage”, respectively, which was concluded from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analyses at each transcriptional phase. Importantly, the differentially expressed genes at 24 h post sciatic nerve transection seemed to be mainly involved in inflammation, which might be a critical process in denervation-induced muscle atrophy. Overall, our study would contribute to the understanding of molecular aspects of denervation-induced muscle atrophy, and may also provide a new insight into the time window for targeted therapy.