RNA 测序揭示了心肌梗死后大鼠膈肌病理重构的转录特征。
RNA-sequencing reveals transcriptional signature of pathological remodeling in the diaphragm of rats after myocardial infarction.
机构信息
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA.
Department of Neurosurgery, University of Florida, Gainesville, FL 32611, USA.
出版信息
Gene. 2021 Feb 20;770:145356. doi: 10.1016/j.gene.2020.145356. Epub 2020 Dec 15.
The diaphragm is the main inspiratory muscle, and the chronic phase post-myocardial infarction (MI) is characterized by diaphragm morphological, contractile, and metabolic abnormalities. However, the mechanisms of diaphragm weakness are not fully understood. In the current study, we aimed to identify the transcriptome changes associated with diaphragm abnormalities in the chronic stage MI. We ligated the left coronary artery to cause MI in rats and performed RNA-sequencing (RNA-Seq) in diaphragm samples 16 weeks post-surgery. The sham group underwent thoracotomy and pericardiotomy but no artery ligation. We identified 112 differentially expressed genes (DEGs) out of a total of 9664 genes. Myocardial infarction upregulated and downregulated 42 and 70 genes, respectively. Analysis of DEGs in the framework of skeletal muscle-specific biological networks suggest remodeling in the neuromuscular junction, extracellular matrix, sarcomere, cytoskeleton, and changes in metabolism and iron homeostasis. Overall, the data are consistent with pathological remodeling of the diaphragm and reveal potential biological targets to prevent diaphragm weakness in the chronic stage MI.
膈是主要的吸气肌，心肌梗死后的慢性期以膈形态、收缩和代谢异常为特征。然而，膈肌无力的机制尚不完全清楚。在本研究中，我们旨在确定与慢性心肌梗死后膈异常相关的转录组变化。我们结扎左冠状动脉造成大鼠心肌梗死，并在手术后 16 周对膈样本进行 RNA 测序（RNA-Seq）。假手术组仅进行开胸和心包切开术，但不结扎动脉。我们在总共 9664 个基因中鉴定出 112 个差异表达基因（DEGs）。心肌梗死分别上调和下调了 42 个和 70 个基因。在骨骼肌特异性生物学网络框架中对 DEGs 的分析表明，神经肌肉接头、细胞外基质、肌节、细胞骨架以及代谢和铁稳态的变化发生了重塑。总的来说，这些数据与膈的病理性重塑一致，并揭示了预防慢性心肌梗死后膈肌无力的潜在生物学靶点。
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