容积性肌肉损失后基因和蛋白质特征的时间动态变化。
Temporal dynamics of gene and protein signatures following volumetric muscle loss.
作者信息
Jain Ishita, Oropeza Beu P, Hu Caroline, Chiang Gladys, Aravindan Sree, Reyes Renato, Li Daniel Yuhang, Cheng Paul, Huang Ngan F
机构信息
Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, United States.
Stanford Cardiovascular Institute, Stanford University, Stanford, CA, United States.
出版信息
Front Cell Dev Biol. 2025 Jul 3;13:1606609. doi: 10.3389/fcell.2025.1606609. eCollection 2025.
INTRODUCTION
Volumetric muscle loss (VML) is characterized by permanent tissue impairment resulting from critically-sized muscle loss. We performed time-series transcriptomic and proteomic analyses to reveal key mediators of irreversible pathological remodeling after induction of VML in mice.
METHODS
The dynamics of gene and protein expression patterns were analyzed for up to 3 weeks after muscle injury.
RESULTS
RNA Sequencing revealed transcriptional patterns that show rapid upregulation or downregulation shortly after injury, among which a subset of genes failed to return to pre-injury levels within 3 weeks after VML. Time-series analysis revealed gene clusters with sustained upregulation after 3 weeks, including those associated with extracellular matrix remodeling and inflammation, whereas the gene clusters having sustained downregulation were associated with mitochondrial function and metabolism. We further identified and as novel molecular mediators of the pathological remodeling process.
DISCUSSION
This work demonstrates the utility of time-series analysis to reveal dysregulated pathways in the setting of VML.
引言
体积性肌肉损失（VML）的特征是由临界大小的肌肉损失导致的永久性组织损伤。我们进行了时间序列转录组学和蛋白质组学分析，以揭示小鼠VML诱导后不可逆病理重塑的关键介质。
方法
在肌肉损伤后长达3周的时间内分析基因和蛋白质表达模式的动态变化。
结果
RNA测序揭示了损伤后不久显示快速上调或下调的转录模式，其中一部分基因在VML后3周内未能恢复到损伤前水平。时间序列分析揭示了3周后持续上调的基因簇，包括那些与细胞外基质重塑和炎症相关的基因簇，而持续下调的基因簇与线粒体功能和代谢相关。我们进一步鉴定了 和 作为病理重塑过程的新型分子介质。
讨论
这项工作证明了时间序列分析在揭示VML背景下失调途径方面的实用性。
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