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Comparative Proteomic and Transcriptomic Analysis of Follistatin-Induced Skeletal Muscle Hypertrophy
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2017-09-07 00:00:00 , DOI: 10.1021/acs.jproteome.7b00069
Caroline Barbé 1 , Fabrice Bray 2 , Marine Gueugneau 1 , Stéphanie Devassine 2 , Pascale Lause 1 , Caroline Tokarski 2 , Christian Rolando 2 , Jean-Paul Thissen 1
Affiliation  

Skeletal muscle, the most abundant body tissue, plays vital roles in locomotion and metabolism. Myostatin is a negative regulator of skeletal muscle mass. In addition to increasing muscle mass, Myostatin inhibition impacts muscle contractility and energy metabolism. To decipher the mechanisms of action of the Myostatin inhibitors, we used proteomic and transcriptomic approaches to investigate the changes induced in skeletal muscles of transgenic mice overexpressing Follistatin, a physiological Myostatin inhibitor. Our proteomic workflow included a fractionation step to identify weakly expressed proteins and a comparison of fast versus slow muscles. Functional annotation of altered proteins supports the phenotypic changes induced by Myostatin inhibition, including modifications in energy metabolism, fiber type, insulin and calcium signaling, as well as membrane repair and regeneration. Less than 10% of the differentially expressed proteins were found to be also regulated at the mRNA level but the Biological Process annotation, and the KEGG pathways analysis of transcriptomic results shows a great concordance with the proteomic data. Thus this study describes the most extensive omics analysis of muscle overexpressing Follistatin, providing molecular-level insights to explain the observed muscle phenotypic changes.

中文翻译:

卵泡抑素诱导的骨骼肌肥大的比较蛋白质组学和转录组学分析

骨骼肌是人体最丰富的组织,在运动和新陈代谢中起着至关重要的作用。肌生长抑制素是骨骼肌质量的负调节剂。除了增加肌肉质量,抑制肌生长抑制素还影响肌肉的收缩力和能量代谢。为解释肌生长抑制素抑制剂的作用机理,我们使用蛋白质组学和转录组学方法研究了过表达生理性肌生长抑制素抑制剂Follistatin的转基因小鼠骨骼肌中诱导的变化。我们的蛋白质组学工作流程包括一个分离步骤,以鉴定弱表达的蛋白质,并比较快肌与慢肌。改变的蛋白质的功能注释支持Myostatin抑制诱导的表型变化,包括能量代谢,纤维类型,胰岛素和钙信号传导的修饰,以及膜修复和再生。发现不到10%的差异表达蛋白在mRNA水平上也受到调节​​,但生物学过程注释和转录组结果的KEGG通路分析表明与蛋白质组学数据高度一致。因此,本研究描述了过度表达卵泡抑素的最广泛的组学分析,提供了分子水平的见解来解释观察到的肌肉表型变化。
更新日期:2017-09-07
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